44 results on '"Pierdominici, Marina"'
Search Results
2. Back to the Future: Is GnRHa Treatment in Transgender and Gender Diverse Adolescents Only an Extended Evaluation Phase?
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Fisher, Alessandra D, Ristori, Jiska, Romani, Alessia, Cassioli, Emanuele, Mazzoli, Francesca, Cocchetti, Carlotta, Pierdominici, Marina, Marconi, Matteo, Ricca, Valdo, Maggi, Mario, Vignozzi, Linda, and Castellini, Giovanni
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WAIST-hip ratio ,DIALECTICAL behavior therapy ,TRANSGENDER people ,GENDER ,PSYCHOLOGICAL tests ,GONADOTROPIN releasing hormone ,TEENAGERS - Abstract
Context The role of body modifications induced by gonadal suppression in transgender and gender diverse adolescents on psychological functioning has not yet been evaluated. Objective The main aim of the present study was to explore several hormone, physical and psychological functioning changes during gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs). The potential relationship between the physical and hormone effects of GnRHa and psychological well-being, along with its magnitude, was assessed for the first time. Methods This prospective multidisciplinary study included 36 TGDA (22 assigned female at birth, and 14 assigned male at birth) who received psychological assessment followed by triptorelin prescription after referring to the Florence Gender Clinic. This study consisted of 3 time points: first referral (T0), psychological assessment (T1); and treatment with intramuscular injections of triptorelin for 3 up to 12 months (T2). Psychometric questionnaires were administered at each time point, and clinical and biochemical evaluations were performed at T1 and T2. Results The following results were found: (1) GnRHa showed efficacy in inhibiting puberty progression in TGDAs; (2) an increase in psychopathology was observed before starting GnRHa (T1) compared with baseline levels; (3) during GnRHa treatment (T2), a significant improvement in psychological functioning, as well as decrease in suicidality, body uneasiness, depression, and anxiety levels were observed; (4) hormone and physical changes (in terms of gonadotropin and sex steroid levels, height and body mass index percentiles, waist–hip ratio, and acne severity) observed during triptorelin treatment significantly correlated with a reduction in suicidal ideation, anxiety, and body image concerns. Conclusion Psychological improvement in TGDA on GnRHa seems to be related to the objective body changes induced by a GnRHa. Therefore, the rationale for treatment with a GnRHa may not only be considered an extension of the evaluation phase, but also the start of a medical (even if reversible) gender-affirming path, especially in TGDAs whose puberty has already progressed. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Hormonal Treatment Effect on Sexual Distress in Transgender Persons: 2-Year Follow-Up Data
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Ristori, Jiska, Cocchetti, Carlotta, Castellini, Giovanni, Pierdominici, Marina, Cipriani, Agnese, Testi, Diletta, Gavazzi, Gioele, Mazzoli, Francesca, Mosconi, Maddalena, Meriggiola, Maria Cristina, Cassioli, Emanuele, Vignozzi, Linda, Ricca, Valdo, Maggi, Mario, and Fisher, Alessandra D.
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- 2020
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4. Autoantibodies specific to a peptide of β2-glycoprotein I cross-react with TLR4, inducing a proinflammatory phenotype in endothelial cells and monocytes
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Colasanti, Tania, Alessandri, Cristiano, Capozzi, Antonella, Sorice, Maurizio, Delunardo, Federica, Longo, Agostina, Pierdominici, Marina, Conti, Fabrizio, Truglia, Simona, Siracusano, Alessandra, Valesini, Guido, Ortona, Elena, and Margutti, Paola
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- 2012
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5. Membrane lipid rafts and estrogenic signalling: a functional role in the modulation of cell homeostasis
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Maselli, Angela, Pierdominici, Marina, Vitale, Cristiana, and Ortona, Elena
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- 2015
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6. Human Monocyte-Derived Dendritic Cells Are the Pharmacological Target of the Immunosuppressant Flavonoid Silibinin.
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Pagano, Maria Teresa, Fecchi, Katia, Pierdominici, Marina, Ortona, Elena, and Peruzzu, Daniela
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FLAVONOIDS ,SILIBININ ,T cells ,MONOCYTES ,AUTOIMMUNE diseases ,THERAPEUTICS ,ANTIGEN presenting cells - Abstract
Silibinin, a natural polyphenolic flavonoid, is known to possess anti-inflammatory, anticancer, antioxidant, and immunomodulatory properties. However, the effects of Silibinin on the maturation and immunostimulatory functions of human dendritic cells (DC) remain to be elucidated. In this study, we have attempted to ascertain whether Silibinin influences the maturation, cytokine production, and antigen-presenting capacity of human monocyte-derived DC. We show that Silibinin significantly suppresses the upregulation of costimulatory and MHC molecules in LPS-stimulated mature DC and inhibits lipopolysaccharide (LPS)-induced interleukin (IL)-12, IL-23, and TNF-α production. Furthermore, Silibinin impairs the proliferation response of the allogenic memory CD4 T lymphocytes elicited by LPS-matured DC and their Th1/Th17 profile. These findings demonstrate that Silibinin displays immunosuppressive activity by inhibiting the maturation and activation of human DC and support its potential application of adjuvant therapy in the treatment of autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Anti-Inflammatory Effects of 1,25(OH)2D/Calcitriol in T Cell Immunity: Does Sex Make a Difference?
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Peruzzu, Daniela, Dupuis, Maria Luisa, Pierdominici, Marina, Fecchi, Katia, Gagliardi, Maria Cristina, Ortona, Elena, and Pagano, Maria Teresa
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CALCITRIOL ,VITAMIN D receptors ,VITAMIN D ,IMMUNITY ,T cells ,RHEUMATOID arthritis - Abstract
Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about the mechanisms underlying this anti-inflammatory effect and the potential sex differences of calcitriol immune regulation. Hence, the aim of this study was to investigate whether calcitriol could act differently in modulating T cell immunity of age-matched male and female healthy donors. We analyzed the effects of calcitriol in T lymphocytes from healthy women and men on the expression levels of the vitamin D receptor (VDR) and pro- and anti-inflammatory cytokine production. We showed that a treatment with calcitriol induced a significant increase in the VDR expression levels of activated T lymphocytes from male and female healthy subjects. Moreover, we found that calcitriol significantly reduced the expression level of pro-inflammatory cytokines IL-17, INF-γ and TNF-α in the T lymphocytes of both sexes. Notably, we observed that calcitriol induced a significant increase in the expression level of anti-inflammatory cytokine IL-10 only in the T lymphocytes from female healthy donors. In conclusion, our study provides new insights regarding the sex-specific anti-inflammatory role of calcitriol in T cell immunity. [ABSTRACT FROM AUTHOR]
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- 2022
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8. Prevalence and Correlates of Sexually Transmitted Infections in Transgender People: An Italian Multicentric Cross-Sectional Study.
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Cocchetti, Carlotta, Romani, Alessia, Mazzoli, Francesca, Ristori, Jiska, Lagi, Filippo, Meriggiola, Maria Cristina, Motta, Giovanna, Pierdominici, Marina, Bartoloni, Alessandro, Vignozzi, Linda, Maggi, Mario, and Fisher, Alessandra Daphne
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The burden of sexually transmitted infections (STIs) in the transgender population remains an underestimated issue. The aims of the present study were to evaluate the prevalence of either self-reported and serological STIs and to describe socio-demographic and clinical characteristics of transgender individuals with STIs. A consecutive series of 705 transgender individuals (assigned-male at birth, AMAB n = 377; assigned-female at birth, AFAB n = 328) referring to six Italian gender clinics were included. Sociodemographic and clinical information was collected during the first visit. In a subsample of 126 individuals prevalence of STIs (human immunodeficiency virus, HIV; hepatitis C, HCV; hepatitis B, HBV; syphilis) were evaluated through serology tests. The self-reported prevalence of HIV, HBV, HCV and syphilis infection in the total sample were 3.4%, 1.6%, 2.6% and 2.0%, respectively. In the subsample who underwent serological tests, higher rates of serological prevalence were found (9.5%, 4.0%, 5.6% and 7.9% for HIV, HBV, HCV and syphilis, respectively). When comparing transgender people with or without self-reported STIs, unemployment, previous incarceration, justice problems and sex work resulted more frequent in the first group (p< 0.03 for all). Regarding health status, we observed higher rates of lifetime substance abuse and psychiatric morbidities in trans people with at least one reported STI (p < 0.05). The prevalence of STIs exceeded that reported in general population and STIs correlates underline the importance of stigma and discrimination as determinants of transgender health. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Persistently biased T-cell receptor repertoires in HIV-1 infected combination antiretroviral therapy-treated patients despite sustained suppression of viral replication
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Giovannetti, Antonello, Pierdominici, Marina, Marziali, Marco, Mazzetta, Francesca, Caprini, Elisabeth, Russo, Giandomenico, Bugarini, Roberto, Bernardi, Maria Livia, Mezzoroma, Ivano, and Aiuti, Fernando
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HIV patients -- Research ,CD4 lymphocytes -- Research ,Highly active antiretroviral therapy -- Observations ,Health - Abstract
Highly active antiretroviral therapy (HAART) reduces plasma viral load to copies/ml and increases CD4 T-cell number and function, in most HIV-1 infected patients. The patients starting with HAART at moderate levels of immunodeficiency have a fully suppressed viral load.
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- 2003
10. Changes in CCR5 and CXCR4 expression and beta-chemokine production in HIV-1-infected patients treated with highly active antiretroviral therapy
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Pierdominici, Marina, Giovannetti, Antonello, Ensoli, Fabrizio, Mazzetta, Francesca, Marziali, Marco, Cristofaro, Maria Rita De, Santini-Muratori, Donatella, Leti, Wilma, and Aiuti, Fernando
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HIV patients -- Care and treatment ,HIV patients -- Research ,Antiviral agents -- Dosage and administration ,Chemokine receptors -- Research ,Health - Published
- 2002
11. Phase II study of sorafenib in patients with relapsed or refractory lymphoma
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Guidetti, Anna, Carlo-Stella, Carmelo, Locatelli, Silvia L., Malorni, Walter, Pierdominici, Marina, Barbati, Cristiana, Mortarini, Roberta, Devizzi, Lilli, Matteucci, Paola, Marchianò, Alfonso, Lanocita, Rodolfo, Farina, Lucia, Dodero, Anna, Tarella, Corrado, Di Nicola, Massimo, Corradini, Paolo, Anichini, Andrea, and Gianni, Alessandro M.
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- 2012
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12. Autoantibodies to estrogen receptor α interfere with T lymphocyte homeostasis and are associated with disease activity in systemic lupus erythematosus
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Colasanti, Tania, Maselli, Angela, Conti, Fabrizio, Sanchez, Massimo, Alessandri, Cristiano, Barbati, Cristiana, Vacirca, Davide, Tinari, Antonella, Chiarotti, Flavia, Giovannetti, Antonello, Franconi, Flavia, Valesini, Guido, Malorni, Walter, Pierdominici, Marina, and Ortona, Elena
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- 2012
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13. Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers.
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Pagano, Maria Teresa, Peruzzu, Daniela, Busani, Luca, Pierdominici, Marina, Ruggieri, Anna, Antinori, Andrea, D'Offizi, Gianpiero, Petrosillo, Nicola, Palmieri, Fabrizio, Piselli, Pierluca, Cicalini, Stefania, Notari, Stefania, Nicastri, Emanuele, Agrati, Chiara, Ippolito, Giuseppe, Vaia, Francesco, Gagliardi, Maria Cristina, Capobianchi, Maria Rosaria, Ortona, Elena, and INMI-ISS COVID-19 team
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LYMPHOCYTE count ,RESPIRATORY insufficiency ,SARS-CoV-2 ,ADULT respiratory distress syndrome ,COVID-19 ,BIOMARKERS ,SEX factors in disease - Abstract
Background: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring. [ABSTRACT FROM AUTHOR]
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- 2021
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14. Skewed T-cell receptor repertoire, decreased thymic output, and predominance of terminally differentiated T cells in ataxia telangiectasia
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Giovannetti, Antonello, Mazzetta, Francesca, Caprini, Elisabetta, Aiuti, Alessandro, Marziali, Marco, Pierdominici, Marina, Cossarizza, Andrea, Chessa, Luciana, Scala, Enrico, Quinti, Isabella, Russo, Giandomenico, and Fiorilli, Massimo
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- 2002
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15. European Surveillance of Immunoglobulin Safety—Results of Initial Survey of 1243 Patients with Primary Immunodeficiencies in 16 Countries
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Quinti, Isabella, Pierdominici, Marina, Marziali, Marco, Giovannetti, Antonello, Donnanno, Simona, Chapel, Helen, Bjorkander, Janne, and Aiuti, Fernando
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- 2002
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16. The role of vitamin D in autoimmune diseases: could sex make the difference?
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Dupuis, Maria Luisa, Pagano, Maria Teresa, Pierdominici, Marina, and Ortona, Elena
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SEX factors in disease ,GENDER differences (Psychology) ,VITAMIN D receptors ,AUTOIMMUNE diseases ,GENDER ,CALCITRIOL ,VITAMIN D - Abstract
Over the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases. [ABSTRACT FROM AUTHOR]
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- 2021
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17. Low-Dose IL-2 Reduces Lymphocyte Apoptosis and Increases Naive CD4 Cells in HIV-1 Patients Treated with HAART
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Pandolfi, Franco, Pierdominici, Marina, Marziali, Marco, Livia Bernardi, Maria, Antonelli, Guido, Galati, Vincenzo, D'Offizi, Gianpiero, and Aiuti, Fernando
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- 2000
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18. Sex Differences in Response to TNF-Inhibiting Drugs in Patients With Spondyloarthropathies or Inflammatory Bowel Diseases.
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Laganà, Bruno, Zullo, Angelo, Scribano, Maria Lia, Chimenti, Maria Sole, Migliore, Alberto, Picchianti Diamanti, Andrea, Lorenzetti, Roberto, Scolieri, Palma, Ridola, Lorenzo, Ortona, Elena, Pierdominici, Marina, and Bruzzese, Vincenzo
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SPONDYLOARTHROPATHIES ,INFLAMMATORY bowel diseases ,INFLAMMATION ,IMMUNE response ,INFLIXIMAB ,ADALIMUMAB - Abstract
Spondyloarthritis (SpA) and inflammatory bowel diseases (IBD) are chronic inflammatory diseases characterized by an aberrant immune response and inflammation with a key role for TNF in their pathogenesis. Accordingly, TNF-inhibiting therapy (TNFi) has dramatically improved the management of these diseases. However, about 30% of patients discontinue TNFi for lack of response, loss of response, and side effects and/or adverse events. Thus, the possibility to identify in advance those patients who will have a good response to TNFi would be extremely beneficial. The aim of this study was to investigate differences between males and females with either SpA or IBD in response to TNFi molecules, i.e., infliximab (IFX) and adalimumab (ADA), considering the reasons for TNFi withdraw. Data of 594 patients, 349 with IBD (M/F: 194/155) and 245 with SpA (M/F: 123/122), previously unexposed to TNFi, were collected. In the IBD group, the rate of female patients discontinuing ADA was significantly higher than that of male patients (p = 0.03). No difference emerged according to the distribution of reason for discontinuation. Otherwise, a similar discontinuation rate between female and male patients receiving IFX therapy was observed. In the SpA group, the overall discontinuation rate was not different between males and females both for ADA and IFX. However, in patients treated with ADA, males interrupted therapy more frequently than females due to lack of response (p = 0.03). In conclusion, the assessment of sex differences in TNFi response could help physicians personalize the therapeutic approach in a sex-oriented perspective. [ABSTRACT FROM AUTHOR]
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- 2019
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19. The Natural Agonist of Estrogen Receptor β Silibinin Plays an Immunosuppressive Role Representing a Potential Therapeutic Tool in Rheumatoid Arthritis.
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Dupuis, Maria Luisa, Conti, Fabrizio, Maselli, Angela, Pagano, Maria Teresa, Ruggieri, Anna, Anticoli, Simona, Fragale, Alessandra, Gabriele, Lucia, Gagliardi, Maria Cristina, Sanchez, Massimo, Ceccarelli, Fulvia, Alessandri, Cristiano, Valesini, Guido, Ortona, Elena, and Pierdominici, Marina
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ESTROGEN receptors ,SILIBININ ,RHEUMATOID arthritis - Abstract
Estrogens, in particular 17β-estradiol (E2), have a strong influence on the immune system and also affect pathological conditions such as autoimmune diseases. The biological effects of E2 are mediated by two intracellular receptors, i.e., estrogen receptor (ER)α and ERβ, which function as ligand-activated nuclear transcription factors producing genomic effects. Immune cells express both ERα and ERβ that play a complex role in modulating inflammation. Phytoestrogens display estrogen-like effects. Among them, silibinin, the major active constituent of silymarin extracted by the milk thistle (Silybum marianum), has been suggested to have an ERβ selective binding. Silibinin is known to have anti-inflammatory, hepatoprotective, and anticarcinogenic effects; however, the role of silibinin in modulating human immune responses and its impact on autoimmunity remains unclear. Aim of this study was to dissect the ability of the ERβ natural ligand silibinin to modulate T cell immunity, taking into account possible differences between females and males, and to define its possible role as therapeutic tool in immune-mediated diseases. To this purpose, female and age-matched male healthy subjects and patients with active rheumatoid arthritis (RA) were recruited. We evaluated the ability of silibinin to modulate ERβ expression in T lymphocytes and its effects on T cell functions (i.e., apoptosis, proliferation, and cytokine production). We also analyzed whether silibinin was able to modulate the expression of microRNA-155 (miR-155), which strongly contributes to the pathogenesis of RA driving aberrant activation of the immune system. We demonstrated that silibinin upregulated ERβ expression, induced apoptosis, inhibited proliferation, and reduced expression of the pro-inflammatory cytokines IL-17 and TNF-α, through ERβ binding, in T lymphocytes from female and male healthy donors. We obtained similar results in T lymphocytes from patients with active RA in term of apoptosis, proliferation, and cytokine production. In addition, we found that silibinin acted as an epigenetic modifier, down-modulating the expression of miR-155. In conclusion, our data demonstrated an immunosuppressive role of silibinin, supporting its application in the treatment of autoimmune diseases as drug, but also as dietary nutritional supplement, opening new perspective in the field of autoimmune disease management. [ABSTRACT FROM AUTHOR]
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- 2018
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20. CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren's syndrome patients and correlates with focus score and disease activity.
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Alessandri, Cristiano, Ciccia, Francesco, Priori, Roberta, Astorri, Elisa, Guggino, Giuliana, Alessandro, Riccardo, Rizzo, Aroldo, Conti, Fabrizio, Minniti, Antonina, Barbati, Cristiana, Vomero, Marta, Pendolino, Monica, Finucci, Annacarla, Ortona, Elena, Colasanti, Tania, Pierdominici, Marina, Malorni, Walter, Triolo, Giovanni, and Valesini, Guido
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- 2017
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21. Distinct Blood and Visceral Adipose Tissue Regulatory T Cell and Innate Lymphocyte Profiles Characterize Obesity and Colorectal Cancer.
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Donninelli, Gloria, Del Cornò, Manuela, Pierdominici, Marina, Scazzocchio, Beatrice, Varì, Rosaria, Varano, Barbara, Pacella, Ilenia, Piconese, Silvia, Barnaba, Vincenzo, D'Archivio, Massimo, Masella, Roberta, Conti, Lucia, and Gessani, Sandra
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COLON cancer diagnosis ,OBESITY ,ADIPOSE tissues ,T cells ,LYMPHOCYTES ,FATTY acids - Abstract
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (T
reg ) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC). Analysis of NK, NKT-like, γδ T, and Treg cell populations in VAT and blood of healthy lean subjects revealed that CD56hi NK and OX40+ Treg cells are more abundant in VAT with respect to blood. Conversely, CD56dim NK and total Treg cells are most present in the circulation, while γδ T lymphocytes are uniformly distributed in the two compartments. Interestingly, a reduced frequency of circulating activated Treg cells, and a concomitant preferential enrichment of OX40- expressing Treg cells in VAT, were selectively observed in obese (Ob) subjects, and directly correlated with body mass index. Likewise, CRC patients were characterized by a specific enrichment of VAT-associated NKT-like cells. In addition, Ob and CRC-affected individuals shared a significant reduction of the Vγ9Vδ2/γδ T cell ratio at systemic level. The alterations in the relative proportions of Treg and NKT-like cells in VAT were found to correlate with the content of pro- and anti-inflammatory polyunsaturated fatty acids (PUFA), respectively. Overall, these results provide evidence for distinct alterations of the immune cell repertoire in the periphery with respect to the VAT microenvironment that uniquely characterize or are shared by different inflammatory conditions, such as obesity and CRC, and suggest that VAT PUFA composition may represent one of the factors that contribute to shape the immune phenotypes. [ABSTRACT FROM AUTHOR]- Published
- 2017
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22. Sex-based differences in autoimmune diseases.
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Ortona, Elena, Pierdominici, Marina, Maselli, Angela, Veroni, Caterina, Aloisi, Francesca, and Shoenfeld, Yehuda
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- 2016
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23. Low expression of estrogen receptor β in T lymphocytes and high serum levels of anti-estrogen receptor a antibodies impact disease activity in female patients with systemic lupus erythematosus.
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Maselli, Angela, Conti, Fabrizio, Alessandri, Cristiano, Colasanti, Tania, Barbati, Cristiana, Vomero, Marta, Ciarlo, Laura, Patrizio, Mario, Romana Spinelli, Francesca, Ortona, Elena, Valesini, Guido, and Pierdominici, Marina
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SYSTEMIC lupus erythematosus diagnosis ,ESTROGEN receptors ,T cells - Abstract
Background: Current evidence indicates that estrogens, in particular 17β-estradiol (E2), play a crucial role in the gender bias of autoimmune diseases although the underlying molecular mechanisms have not yet been fully elucidated. Immune cells have estrogen receptors (ERs), i.e., ERα and ERβ, that play pro- and anti- inflammatory functions, respectively, and the presence of one estrogen receptor (ER) subtype over the other might change estrogen effects, promoting or dampening inflammation. In this study, we contributed to define the influences of E2 on T cells from female patients with systemic lupus erythematosus (SLE), a representative autoimmune disease characterized by a higher prevalence in women than in men (female/male ratio 9:1). Particularly, our aim was to evaluate whether alterations of ERα and ERβ expression in T cells from female SLE patients may impact lymphocyte sensitivity to E2 and anti-ERα antibody (anti-ERα Ab) stimulation interfering with cell signaling and display a direct clinical effect. Methods: Sixty-one premenopausal female patients with SLE and 40 age-matched healthy donors were recruited. Patients were divided into two groups based on the SLE Disease Activity Index 2000 (SLEDAI-2K) (i.e., <6 and ≥6). ER expression was evaluated in T lymphocytes by flow cytometry, immunofluorescence, and Western blot analyses. Serum anti-ERα Ab levels were analyzed by enzyme-linked immunosorbent assay (ELISA). ER-dependent signaling pathways were measured by a phosphoprotein detection kit. Results: Intracellular ERβ expression was significantly lower in T cells from patients with SLEDAI-2K ≥6 as compared with healthy donors and patients with SLEDAI-2K <6 and negatively correlated with disease activity. The expression of intracellular and membrane-associated-ERα was similar in SLE and control T cells. ER-dependent signaling pathways were activated in T cells from SLE patients with SLEDAI-2K ≥6, but not with SLEDAI-2K <6, when both membrane and intracellular ERs were stimulated by co-treatment with E2 and anti-ERα Abs. Conclusions: Our results demonstrate an altered ER profile in SLE patients, possibly contributing to SLE pathogenesis and interfering with clinical activity, and highlight the potential exploitation of T cell-associated ERβ as a biomarker of disease activity. [ABSTRACT FROM AUTHOR]
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- 2016
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24. Diesel exhaust particle exposure in vitro impacts T lymphocyte phenotype and function.
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Pierdominici, Marina, Maselli, Angela, Cecchetti, Serena, Tinari, Antonella, Mastrofrancesco, Arianna, Alfè, Michela, Gargiulo, Valentina, Beatrice, Carlo, Di Blasio, Gabriele, Carpinelli, Giulia, Ortona, Elena, Giovannetti, Antonello, and Fiorito, Silvana
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AIR pollution ,HEALTH ,DIESEL motor exhaust gas ,T cells ,AUTOPHAGY ,MITOCHONDRIA ,INTERLEUKIN-2 - Abstract
Background Diesel exhaust particles (DEP) are major constituents of ambient air pollution and their adverse health effect is an area of intensive investigations. With respect to the immune system, DEP have attracted significant research attention as a factor that could influence allergic diseases interfering with cytokine production and chemokine expression. With this exception, scant data are available on the impact of DEP on lymphocyte homeostasis. Here, the effects of nanoparticles from Euro 4 (E4) and Euro 5 (E5) light duty diesel engines on the phenotype and function of T lymphocytes from healthy donors were evaluated. Methods T lymphocytes were isolated from peripheral blood obtained from healthy volunteers and subsequently stimulated with different concentration (from 0.15 to 60 µg/ml) and at different time points (from 24 h to 9 days) of either E4 or E5 particles. Immunological parameters, including apoptosis, autophagy, proliferation levels, mitochondrial function, expression of activation markers and cytokine production were evaluated by cellular and molecular analyses. Results DEP exposure caused a pronounced autophagic-lysosomal blockade, thus interfering with a key mechanism involved in the maintaining of T cell homeostasis. Moreover, DEP decreased mitochondrial membrane potential but, unexpectedly, this effect did not result in changes of the apoptosis and/or necrosis levels, as well as of intracellular content of adenosine triphosphate (ATP). Finally, a down-regulation of the expression of the alpha chain of the interleukin (IL)-2 receptor (i.e., the CD25 molecule) as well as an abnormal Th1 cytokine expression profile (i.e., a decrease of IL-2 and interferon (IFN)-γ production) were observed after DEP exposure. No differences between the two compounds were detected in all studied parameters. Conclusions Overall, our data identify functional and phenotypic T lymphocyte parameters as relevant targets for DEP cytotoxicity, whose impairment could be detrimental, at least in the long run, for human health, favouring the development or the progression of diseases such as autoimmunity and cancer. [ABSTRACT FROM AUTHOR]
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- 2014
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25. Autoantibodies to estrogen receptors and their involvement in autoimmune diseases and cancer.
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Ortona, Elena, Pierdominici, Marina, and Berstein, Lev
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AUTOANTIBODIES , *ESTROGEN receptors , *AUTOIMMUNE diseases , *BREAST cancer , *CELLULAR signal transduction , *TRANSCRIPTION factors - Abstract
The involvement of estrogens, which influence many physiologic processes, has been shown in the development or progression of several diseases including some cancers, most notably breast cancer, and autoimmune disorders. Estrogenic signal is transferred via estrogen receptors (ER) which have dual localization, predominantly intracellular but also in plasma membrane. The discovery of membrane-associated ER (mER) has greatly expanded our understanding of estrogen action; upon ligand binding, mER rapidly activate different signaling pathways inducing downstream transcription factors. Some target genes of the mER pathway may be activated independently of the intracellular ER. Additionally, intracellular ER action can be modulated by mER-initiated signaling. Most notably, the identification of autoantibodies reacting with ER (ERAB) and their possible pathogenic role in autoimmunity and cancer have opened a new path for the research in the estrogen-related receptor activity. In this review, we briefly recapitulate the localization and function of ER and mostly discuss the possible role of ERAB as novel potential prognostic and/or predictive tools in autoimmunity and cancer. [ABSTRACT FROM AUTHOR]
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- 2014
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26. Relationship Between Redox Status and Cell Fate in Immunity and Autoimmunity.
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Ortona, Elena, Maselli, Angela, Delunardo, Federica, Colasanti, Tania, Giovannetti, Antonello, and Pierdominici, Marina
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- 2014
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27. Autophagy as a pathogenic mechanism and drug target in lymphoproliferative disorders.
- Author
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Pierdominici, Marina, Barbati, Cristiana, Vomero, Marta, Locatelli, Silvia L., Carlo-Stella, Carmelo, Ortona, Elena, and Malorni, Walter
- Subjects
- *
AUTOPHAGY , *LYMPHOPROLIFERATIVE disorders , *ORGANELLES , *LYSOSOMES , *DISEASE progression , *CANCER treatment , *THERAPEUTICS - Abstract
Autophagy represents a key mechanism of cytoprotection that can be activated by a variety of extracellular and intracellular stresses and allows the cell to sequester cytoplasmic components and damaged organelles, delivering them to lysosomes for degradation and recycling. However, the autophagy process has also been associated with the death of the cell. It has been demonstrated to be constitutive in some instances and inducible in others, and the idea that it could represent a pathogenetic determinant as well as a possible prognostic tool and a therapeutic target in a plethora of human diseases has recently been considered. Among these, cancer represents a major one. In this review, we recapitulate the critical implications of autophagy in the pathogenesis, progression, and treatment of lymphoproliferative disorders. Leukemias and lymphomas, in fact, represent paradigmatic human diseases in which advances have recently been made in this respect. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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28. Autoantibodies to Estrogen Receptor α in Systemic Sclerosis (SSc) as Pathogenetic Determinants and Markers of Progression.
- Author
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Giovannetti, Antonello, Maselli, Angela, Colasanti, Tania, Rosato, Edoardo, Salsano, Felice, Pisarri, Simonetta, Mezzaroma, Ivano, Malorni, Walter, Ortona, Elena, and Pierdominici, Marina
- Subjects
AUTOIMMUNE disease treatment ,AUTOANTIBODIES ,ESTROGEN receptors ,SYSTEMIC scleroderma ,ETIOLOGY of diseases ,T cells ,IMMUNE system - Abstract
Systemic sclerosis (SSc) is a multisystem autoimmune disease of unknown etiology characterized by inflammation, autoantibody production, and fibrosis. It predominantly affects women, this suggesting that female sex hormones such as estrogens may play a role in disease pathogenesis. However, up to date, the role of estrogens in SSc has been scarcely explored. The activity of estrogens is mediated either by transcription activity of the intracellular estrogen receptors (ER), ERα and ERβ, or by membrane-associated ER. Since the presence of autoantibodies to ERα and their role as estrogen agonists interfering with T lymphocyte homeostasis were demonstrated in other autoimmune diseases, we wanted to ascertain whether anti-ERα antibodies were detectable in sera from patients with SSc. We detected anti-ERα antibody serum immunoreactivity in 42% of patients with SSc (30 out of 71 analyzed). Importantly, a significant association was found between anti-ERα antibody values and key clinical parameters of disease activity and severity. Fittingly, anti-ERα antibody levels were also significantly associated with alterations of immunological features of SSc patients, including increased T cell apoptotic susceptibility and changes in T regulatory cells (Treg) homeostasis. In particular, the percentage of activated Treg (CD4
+ CD45RA− FoxP3bright CD25bright ) was significantly higher in anti-ERα antibody positive patients than in anti-ERα antibody negative patients. Taken together our data clearly indicate that anti-ERα antibodies, probably via the involvement of membrane-associated ER, can represent: i) promising markers for SSc progression but, also, ii) functional modulators of the SSc patients’ immune system. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
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29. T lymphocytes from patients with systemic lupus erythematosus are resistant to induction of autophagy.
- Author
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Alessandri, Cristiano, Barbati, Cristiana, Vacirca, Davide, Piscopo, Paola, Confaloni, Annamaria, Sanchez, Massimo, Maselli, Angela, Colasanti, Tania, Conti, Fabrizio, Truglia, Simona, Perl, Andras, Valesini, Guido, Malorni, Walter, Ortona, Elena, and Pierdominici, Marina
- Subjects
T cells ,SYSTEMIC lupus erythematosus ,AUTOPHAGY ,AUTOIMMUNITY ,CELL determination ,CELL differentiation ,AUTOANTIBODIES - Abstract
Autophagy, the cytoprotection mechanism that takes place under metabolic impairment, has been implicated in the pathogenesis of autoimmunity. Here, we investigated the spontaneous and induced autophagic behavior of T lymphocytes from patients with systemic lupus erythematosus (SLE) compared with that of T lymphocytes from healthy donors by measuring the autophagy marker microtubule-associated protein 1 light chain 3 (LC3)-II. No significant differences in spontaneous autophagy were found between T lymphocytes from patients with SLE and from healthy donors, apart from CD4
+ naive T cells from patients with SLE in which constitutively higher levels of autophagy (P<0.001) were detected. At variance, whereas treatment of T lymphocytes from healthy donors with serum IgG from patients with SLE resulted in a 2-fold increase in LC3-II levels (P<0.001), T lymphocytes from SLE patients were resistant to autophagic induction and also displayed an up-regulation of genes negatively regulating autophagy, e.g., α-synuclein. These findings could open new perspectives in the search for pathogenetic determinants of SLE progression and in the development of therapeutic strategies aimed to recover T-cell compartment homeostasis by restoring autophagic susceptibility. [ABSTRACT FROM AUTHOR]- Published
- 2012
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- View/download PDF
30. Cell Surface Estrogen Receptor Alpha Is Upregulated during Subchronic Metabolic Stress and Inhibits Neuronal Cell Degeneration.
- Author
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Barbati, Cristiana, Pierdominici, Marina, Gambardella, Lucrezia, Albedi, Fiorella Malchiodi, Karas, Richard H., Rosano, Giuseppe, Malorni, Walter, and Ortona, Elena
- Subjects
- *
CELLULAR mechanics , *STEROID receptors , *CELL membranes , *APOPTOSIS , *MOLECULAR chaperones , *ESTROGEN receptors , *NEURODEGENERATION - Abstract
In addition to the classical nuclear estrogen receptor, the expression of non-nuclear estrogen receptors localized to the cell surface membrane (mER) has recently been demonstrated. Estrogen and its receptors have been implicated in the development or progression of numerous neurodegenerative disorders. Furthermore, the pathogenesis of these diseases has been associated with disturbances of two key cellular programs: apoptosis and autophagy. An excess of apoptosis or a defect in autophagy has been implicated in neurodegeneration. The aim of this study was to clarify the role of ER in determining neuronal cell fate and the possible implication of these receptors in regulating either apoptosis or autophagy. The human neuronal cell line SH-SY5Y and mouse neuronal cells in primary culture were thus exposed to chronic minimal peroxide treatment (CMP), a form of subcytotoxic minimal chronic stress previously that mimics multiple aspects of longterm cell stress and represents a limited molecular proxy for neurodegenerative processes. We actually found that either E2 or E2-bovine serum albumin construct (E2BSA, i.e. a non-permeant form of E2) was capable of modulating intracellular cell signals and regulating cell survival and death. In particular, under CMP, the up-regulation of mERα, but not mERb, was associated with functional signals (ERK phosphorylation and p38 dephosphorylation) compatible with autophagic cytoprotection triggering and leading to cell survival. The mERα trafficking appeared to be independent of the microfilament system cytoskeletal network but was seemingly associated with microtubular apparatus network, i.e., to MAP2 molecular chaperone. Importantly, antioxidant treatments, administration of siRNA to ERα, or the presence of antagonist of ERα hindered these events. These results support that the surface expression of mERα plays a pivotal role in determining cell fate, and that ligand-induced activation of mER signalling exerts a powerful cell-survival signal. These results shed new light on the pathogenetic mechanisms leading to neuronal cell degeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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31. Role of autophagy in immunity and autoimmunity, with a special focus on systemic lupus erythematosus.
- Author
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Pierdominici, Marina, Vomero, Marta, Barbati, Cristiana, Colasanti, Tania, Maselli, Angela, Vacirca, Davide, Giovannetti, Antonello, Malorni, Walter, and Ortona, Elena
- Subjects
- *
AUTOPHAGY , *LYSOSOMES , *IMMUNE response , *SYSTEMIC lupus erythematosus , *VASCULAR diseases - Abstract
Autophagy is a lysosome-mediated catabolic process that allows cells to degrade unwanted cytoplasmic constituents and to recycle nutrients. Autophagy is also involved in innate and adaptive immune responses, playing a key role in interactions against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. Over recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmunity. Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by autoimmune responses against self-antigens generated by dying cells. Genome-wide association studies have linked several single-nucleotide polymorphisms (SNPs) in the autophagy-related gene Atg5 to SLE susceptibility. Loss of Atg5-dependent effects, including clearance of dying cells and cell antigen presentation, might contribute to the autoimmunity and inflammation associated with SLE. Moreover, activation of the mammalian target of rapamycin (mTOR), a key player in the autophagy regulation, has recently been demonstrated in SLE, confirming an altered autophagy pathway in this disease. In the present review, we summarize the autophagy mechanisms, their molecular regulation, and their relevance in immunity and autoimmunity. The potential of targeting autophagy pathway in SLE, by developing innovative therapeutic approaches, has finally been discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
32. Estrogen receptor profiles in human peripheral blood lymphocytes
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Pierdominici, Marina, Maselli, Angela, Colasanti, Tania, Giammarioli, Anna Maria, Delunardo, Federica, Vacirca, Davide, Sanchez, Massimo, Giovannetti, Antonello, Malorni, Walter, and Ortona, Elena
- Subjects
- *
ESTRADIOL , *ESTROGEN receptors , *LYMPHOCYTES , *IMMUNOREGULATION , *PROTEIN kinases , *WESTERN immunoblotting , *KILLER cells - Abstract
Abstract: Estrogens are well-known regulators of the immune responses. Most of their effects are mediated by two receptors: estrogen receptor (ER)α and ERβ. Up to date the presence of intracellular ER in human immune cells represents a controversial issue, while their surface membrane expression has scarcely been explored. In this study we investigated the intracellular and cell surface expression of ERα and ERβ in human peripheral blood lymphocytes (PBL) by flow and static cytometry as well as by Western Blot. To this aim we used five different commercial antibodies recognizing distinct ER epitopes. We observed that CD4+ and CD8+ T lymphocytes, B lymphocytes and NK cells contain intracellular ERα and ERβ, being the ERα46 isoform the most represented ER. However, significant differences could be observed among the antibodies studied in terms of immunoreactivity and specificity. Importantly, we also found a cell surface expression of ERα46 isoform. We also observed that a membrane-impermeant form of E2 induced a rapid phosphorylation of extracellular signal-regulated kinase (ERK), a significant proliferation of T lymphocytes, and IFN-γ production by NK cells, thus suggesting the expression of a functional mERα. In conclusion our data could provide new insights as concerns the estrogen-related mechanisms of immune system modulation. They also suggest the need for a reappraisal of the experimental conditions for the characterization of the ER expression. [Copyright &y& Elsevier]
- Published
- 2010
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33. Progressive Derangement of the T Cell Compartment in a Case of Evans Syndrome.
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Giovannetti, Antonello, Pierdominici, Marina, Esposito, Antonella, Cagliuso, Maria, Stifano, Giuseppina, Giammarioli, Anna Maria, Maselli, Angela, Malorni, Walter, Salsano, Felice, and Aiuti, Fernando
- Subjects
- *
AUTOIMMUNE hemolytic anemia , *T cells , *B cells , *CYTOKINES , *CELLULAR immunity - Abstract
Background: Evans syndrome (ES) is a rare disorder characterized by combined autoimmune thrombocytopenia and autoimmune hemolytic anemia. Several studies have documented a number of B cell defects, whereas only limited information is currently available about the T cell subset. Methods: A wide panel of immunological analyses aiming specifically at a quantitative and qualitative evaluation of the T cell compartment was performed in an unusual case of ES. The peripheral distribution of the T cell subsets, the diversity of the T cell receptor (TCR) repertoires, the cytokine profile and the T cell apoptosis have been longitudinally evaluated. Results: On first investigation, flow-cytometric immunophenotyping showed a remarkable alteration of T cell homeostasis with deeply reduced CD4+ naive T cells and recent thymic emigrants. This was seen in association with increased levels of T cell activation and apoptosis. Consistently with these data the cytokine profile was characterized by high interferon-γ and low interleukin-2 levels. Staining for CD4 and CD25 molecules showed decreased percentages of circulating regulatory T cells according to the autoimmune nature of ES. Finally, restricted TCR repertoires were demonstrated by a skewed TCR β chain variable (TCRBV) gene usage as well as oligoclonal third complementarity- determining region (CDR3) profiles. A deterioration of the above-mentioned parameters and a worsening of the clinical condition were observed during the follow-up requiring more intensive treatments. Conclusion: The demonstration of multiple T cell defects, in addition to providing pathogenetic information, is likely to alter both acute treatment and outcome of ES. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
- Published
- 2008
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- View/download PDF
34. Chemokines in human immunodeficiency virus (HIV) infection.
- Author
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Giovannetti, Antonello and Pierdominici, Marina
- Subjects
- *
CHEMOKINES , *HIV infections , *DRUG dosage , *LIGANDS (Biochemistry) , *DISEASES - Abstract
The article focuses on chemokines in human immunodeficiency virus (HIV) infection. It discusses the three hypotheses that may be made to explain how high doses of CC chemokine ligand 3-like 1 (CCL3LI) would contrast the infection of disease progression. The authors believe that the role of CC chemokines in HIV-1 infection can be clearly demonstrated through an extremely well defined population of subjects in which the highest number of contributing factors could be standardized.
- Published
- 2008
35. Changes in CCR5 and CXCR4 Expression and β -Chemokine Production in HIV-1-Infected Patients Treated With Highly Active Antiretroviral Therapy.
- Author
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Pierdominici, Marina, Giovannetti, Antonello, Ensoli, Fabrizio, Mazzetta, Francesca, Marziali, Marco, De Cristofaro, Maria Rita, Santini-Muratori, Donatella, Leti, Wilma, and Aiuti, Fernando
- Subjects
- *
CHEMOKINES , *HIV-positive persons , *T cells , *CD4 antigen , *IMMUNOLOGY - Abstract
Investigates the effect of highly active antiretroviral therapy (HAART) on the expression of CCR5 and CXCR4 HIV coreceptors in HIV-infected individuals. Analysis of the virologic and immunologic parameters; Distribution of naive and memory cells and levels of immune activation markers; CD4 and CD8 T cell subsets before and after therapy; Measurements of spontaneous and lectin-induced chemokine production.
- Published
- 2002
- Full Text
- View/download PDF
36. Synergy Between Vitamin D and Sex Hormones in Respiratory Functionality of Patients Affected by COVID-19.
- Author
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Peruzzu, Daniela, Pagano, Maria Teresa, Pierdominici, Marina, Ruggieri, Anna, Antinori, Andrea, D'Offizi, Gianpiero, Petrosillo, Nicola, Palmieri, Fabrizio, Piselli, Pierluca, Boumis, Evangelo, Notari, Stefania, Nicastri, Emanuele, Agrati, Chiara, Ippolito, Giuseppe, Gagliardi, Maria Cristina, Capobianchi, Maria Rosaria, and Ortona, Elena
- Subjects
SEX hormones ,VITAMIN D ,COVID-19 ,OLDER women ,OLDER men ,AGE differences ,OLDER patients ,WOMEN patients - Abstract
The outcome of COVID-19 appears to be influenced by vitamin D status of population. Although epidemiological data indicate that COVID-19 produces more severe symptoms and higher mortality in elderly in comparison to young patients and in men in comparison to women to date sex and age differences in vitamin D status in infected patients have not been evaluated yet. In this study we evaluated the levels of circulating 25(OH)D in patients hospitalized for COVID-19 divided accordingly to their sex and age. We also correlated 25(OH)D levels with patient's respiratory status (i.e., PaO2/FiO2 ratio) and with sex hormones plasma levels to analyze the potential relationship of these parameters. We found no significant differences in plasma levels of 25(OH)D between pre- and post-menopausal female patients and age matched male patients. Interestingly, the 25(OH)D plasma levels positively correlated to PaO2/FiO2 ratio only in young patients, regardless of their sex. We also found a significantly positive correlation between 17β-estradiol and 25(OH)D in elderly women and between testosterone and 25(OH)D in elderly men, supporting the role of sex hormones in maintaining 25(OH)D levels. In conclusion, we suggest that a synergy between vitamin D and sex hormones could contribute to the age-related outcome of COVID-19. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
37. Prolif erative Responses to PHA, Anti-CD3 and Antigens in Patients with Lymphoproliferative Disease of Granular Lymphocytes.
- Author
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Giovannetti, Antonello, Quinti, Isabella, Rainaldi, Luana, Maur, Francesca R., Oliva, Alessandra, Pierdominici, Marina, Ricci, Giovanni, Rossi, Giulio De, Cassone, Antonio, Aiuti, Fernando, and Pandolfi, Franco
- Published
- 1997
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- View/download PDF
38. Examining the training needs and perspectives of Italian general practitioners on transgender and gender diverse healthcare: Insights from a national survey.
- Author
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Marconi, Matteo, Brogonzoli, Luisa, Ruocco, Angela, Sala, Elisa, D’Arienzo, Sara, Manoli, Martina, Pagano, Maria Teresa, Fisher, Alessandra Daphne, Iardino, Rosaria, Pedale, Rosa, Grattagliano, Ignazio, Cricelli, Claudio, and Pierdominici, Marina
- Published
- 2024
- Full Text
- View/download PDF
39. Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer.
- Author
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Maselli, Angela, Parlato, Stefania, Puglisi, Rossella, Raggi, Carla, Spada, Massimo, Macchia, Daniele, Pontecorvi, Giada, Iessi, Elisabetta, Pagano, Maria Teresa, Cirulli, Francesca, Gabriele, Lucia, Carè, Alessandra, Vici, Patrizia, Pizzuti, Laura, Barba, Maddalena, Matarrese, Paola, Pierdominici, Marina, and Ortona, Elena
- Subjects
AUTOANTIBODIES ,HORMONE receptor positive breast cancer - Abstract
Tamoxifen resistance is a major hurdle in the treatment of estrogen receptor (ER)-positive breast cancer. The mechanisms of tamoxifen resistance are not fully understood although several underlying molecular events have been suggested. Recently, we identified autoantibodies reacting with membrane-associated ERα (anti-ERα Abs) in sera of breast cancer patients, able to promote tumor growth. Here, we investigated whether anti-ERα Abs purified from sera of ER-positive breast cancer patients could contribute to tamoxifen resistance. Anti-ERα Abs inhibited tamoxifen-mediated effects on cell cycle and proliferation in MCF-7 cells. Moreover, anti-ERα Abs hampered the tamoxifen-mediated reduction of tumor growth in SCID mice xenografted with breast tumor. Notably, simvastatin-mediated disaggregation of lipid rafts, where membrane-associated ERα is embedded, restored tamoxifen sensitivity, preventing anti-ERα Abs effects. In conclusion, detection of serum anti-ERα Abs may help predict tamoxifen resistance and concur to appropriately inform therapeutic decisions concerning hormone therapy in ER-positive breast cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
40. Autoantibodies specific to estrogen receptor alpha act as estrogen agonists and their levels correlate with breast cancer cell proliferation.
- Author
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Maselli, Angela, Capoccia, Sara, Pugliese, Patrizia, Raggi, Carla, Cirulli, Francesca, Fabi, Alessandra, Malorni, Walter, Pierdominici, Marina, and Ortona, Elena
- Subjects
ESTROGEN receptors ,AUTOANTIBODIES ,CELL membranes ,NUCLEAR receptors (Biochemistry) ,BREAST cancer ,CANCER cell proliferation - Abstract
Estrogen receptors have recently been demonstrated at the cell surface. Unlike nuclear receptors, they are able to trigger rapid responses inside the cells. In this study, we evaluated the presence and the possible role of autoantibodies specific to estrogen receptor (anti-ER Abs) in the peripheral blood of breast cancer patients. Anti-ERα Abs were detectable in 22/48 (46%) patients' sera and their levels positively correlated with the percentage of Ki-67-positive breast cancer cells. Anti-ERα Abs purified from breast cancer patients' sera were able: (i) to recognize ERα epitopes expressed at the cell surface of ER-positive breast cancer cells, (ii) to trigger rapid extracellular signal-regulated kinase (ERK) phosphorylation, and (iii) to induce cell proliferation. Our results suggest that anti-ERα Abs can act as estrogen agonists playing a pathogenetic role as breast cancer-promoting factors. These autoantibodies could also be considered as possible peripheral blood biomarkers indicative of the breast cancer growth potential. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
- View/download PDF
41. Apoptosis in asymptomatic HIV-1 seropositives immunized with HIV-1 env glycoprotein (gp160): Effects of administration of Zidovudine in vivo and interleukin-2 in vitro
- Author
-
Pierdominici, Marina, Mollicone, Bianca, Ricci, Giovanni, Oliva, Alessandra, D'Offizi, Gianpiero, Giovannetti, Antonello, Aiuti, Fernando, and Pandolfi, Franco
- Published
- 1998
- Full Text
- View/download PDF
42. Autoantibodies specific to D4GDI modulate Rho GTPase mediated cytoskeleton remodeling and induce autophagy in T lymphocytes.
- Author
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Barbati, Cristiana, Alessandri, Cristiano, Vomero, Marta, Vona, Rosa, Colasanti, Tania, Vacirca, Davide, Camerini, Serena, Crescenzi, Marco, Pendolino, Monica, Truglia, Simona, Conti, Fabrizio, Garofalo, Tina, Sorice, Maurizio, Pierdominici, Marina, Valesini, Guido, Malorni, Walter, and Ortona, Elena
- Subjects
- *
AUTOANTIBODIES , *RECOMBINANT proteins , *RHO GTPases , *CYTOSKELETON , *TISSUE remodeling , *AUTOPHAGY , *T cells - Abstract
T lymphocytes from patients with Systemic Lupus Erythematosus (SLE) display multiple abnormalities, including increased cell activation, abnormal cell death by apoptosis and impairment of autophagy pathway. In the present study we report the presence of specific antibodies to D4GDI, a small GTPase family inhibitor, in a significant percentage (46%) of SLE patient sera. We also found a significant association between the presence of these autoantibodies and hematologic manifestations occurring in these patients. Investigating the possible implication of anti-D4GDI autoantibodies in SLE pathogenesis or progression, we found that these antibodies were capable of binding D4GDI expressed at the lymphocyte surface and triggering a series of subcellular events, including Rho GTPase activation. These antibodies were also able to induce autophagy in T cells from both healthy donors and SLE patients, but only those negative to these antibodies. We can conclude that anti-D4GDI autoantibodies could be capable of triggering important responses in T cells such as cytoskeleton remodeling and autophagy pathway and that, in SLE patients, the chronic exposure to these specific autoantibodies could lead to the selection of autophagy-resistant T cell clones contributing to the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
43. Autoantibodies specific to a peptide of β2-glycoprotein I cross-react with TLR4, inducing a proinflammatory phenotype in endothelial cells and monocytes.
- Author
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Colasanti, Tania, Alessandri, Cristiano, Capozzi, Antonella, Sorice, Maurizio, Delunardo, Federica, Longo, Agostina, Pierdominici, Marina, Conti, Fabrizio, Truglia, Simona, Siracusano, Alessandra, Valesini, Guido, Ortona, Elena, and Margutti, Paola
- Subjects
- *
AUTOANTIBODIES , *GLYCOPROTEINS , *TOLL-like receptors , *ENDOTHELIAL cells , *MONOCYTES , *PHENOTYPES , *THROMBOSIS - Abstract
β2-glycoprotein I (β2GPI) Is the major anti-genic target for antlphospholipid Abs. Anti-β2GPI Abs are a heterogeneous population of Igs targeting all domains of the molecule. Abs specific to β2GPI do-main I are strongly associated with throm-bosis and obstetric complications. In the present study, we sought to understand the possible pathogenic mechanism for this subset of anti-β2GPI Abs, investigat-ing their potential cross-reactivity with other self-proteins involved in inflamma-tory or coagulant events. We compared the amino acid sequence of the β2GPI domain I with human proteins In a protein databank and identified a peptide sharing 88% identity with an epitope of human TLR4. A high percentage of patients with antiphospholipid syndrome (41%) and systemic lupus erythematosus (50%) pre-sented serum IgG specific to this peptide. Anti-β2GPI peptide Abs binding the TLR4 were able to Induce NF-KB activation in HEK293 cells that were stably transfected with the TLR4 gene. Anti-β2GPI peptide Abs induced activation of TLR4 and trig-gered interleukin-1 receptor-associated ki-nase phosphorylation and NF-KB translo-cation, promoting VCAM expression on endothelial cells and TNF-α release by monocytes. In conclusion, our observa-tions suggest a novel pathogenic mecha-nism in the TLR4 stimulation by antl-β2GPI peptide Abs that links adaptive immune responses with Innate immunity In antlphospholipid syndrome and sys-temic lupus erythematosus. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
44. Analyses of T cell phenotype and function reveal an altered T cell homeostasis in systemic sclerosis: Correlations with disease severity and phenotypes
- Author
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Giovannetti, Antonello, Rosato, Edoardo, Renzi, Cristina, Maselli, Angela, Gambardella, Lucrezia, Giammarioli, Anna Maria, Palange, Paolo, Paoletti, Patrizia, Pisarri, Simonetta, Salsano, Felice, Malorni, Walter, and Pierdominici, Marina
- Subjects
- *
T cells , *HOMEOSTASIS , *SYSTEMIC scleroderma , *LYMPHOCYTES , *APOPTOSIS , *CELL proliferation , *THYMUS - Abstract
Abstract: We investigated in systemic sclerosis (SSc) patients the T cell homeostasis and its relationship with the clinical course of the disease. Distribution of peripheral T cell subsets, thymic output, lymphocyte proliferation and apoptosis were analyzed by flow cytometry or ELISA. Age inappropriate levels of naive CD4+ T cells and thymic output were observed. Proliferation of CD4+ T cells, lymphocyte apoptosis and CD4+ regulatory T (Treg) cell frequency were significantly higher than those observed in controls and significantly correlated with clinical phenotypes and clinical progression parameters i.e., diffusing capacity of the lung for carbon monoxide (DLCO) and disease activity. These data indicate that the evaluation of the T cell homeostasis can represent a valuable prognostic tool for SSc patients and it is useful to distinguish between limited and diffuse phenotypes. A therapeutic intervention targeted at reversing T cell homeostasis abnormalities would therefore potentially be helpful in counteracting disease progression. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
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