8 results on '"Fabio LM. Ricciardolo"'
Search Results
2. A microRNA-21–mediated SATB1/S100A9/NF-κB axis promotes chronic obstructive pulmonary disease pathogenesis
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Andrew G. Jarnicki, Guy Brusselle, Philip M. Hansbro, Paul S. Foster, Peter A. B. Wark, Griet Conickx, Gaetano Caramori, Pieter Mestdagh, Fabio Lm Ricciardolo, Alan Hsu, Gang Liu, Krishna P. Sunkara, Emma L. Beckett, Sara R.A. Wijnant, Jay C. Horvat, Antonio Ieni, Izabela Galvão, Chantal Donovan, Richard Kim, Tatt Jhong Haw, Angela Ferguson, Antonino Di Stefano, Umamainthan Palendira, and Ken R. Bracke
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Pulmonary disease ,S100A9 ,Pathogenesis ,Mice ,Pulmonary Disease, Chronic Obstructive ,chemistry.chemical_compound ,microRNA ,medicine ,Animals ,Calgranulin B ,Lung ,ComputingMilieux_MISCELLANEOUS ,COPD ,Inhalation ,business.industry ,NF-kappa B ,COPD, NF-kB ,NF-κB ,Matrix Attachment Region Binding Proteins ,General Medicine ,SATB1 ,medicine.disease ,MicroRNAs ,chemistry ,Immunology ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,06 Biological Sciences, 11 Medical and Health Sciences ,business - Abstract
Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death worldwide. Inhalation of cigarette smoke (CS) is the major cause in developed countries. Current therapies have limited efficacy in controlling disease or halting its progression. Aberrant expression of microRNAs (miRNAs) is associated with lung disease, including COPD. We performed miRNA microarray analyses of the lungs of mice with CS-induced experimental COPD. miR-21 was the second highest up-regulated miRNA, particularly in airway epithelium and lung macrophages. Its expression in human lung tissue correlated with reduced lung function in COPD. Prophylactic and therapeutic treatment with a specific miR-21 inhibitor (Ant-21) inhibited CS-induced lung miR-21 expression in mice; suppressed airway macrophages, neutrophils, and lymphocytes; and improved lung function, as evidenced by decreased lung hysteresis, transpulmonary resistance, and tissue damping in mouse models of COPD. In silico analyses identified a potential miR-21/special AT-rich sequence–binding protein 1 (SATB1)/S100 calcium binding protein A9 (S100A9)/nuclear factor κB (NF-κB) axis, which was further investigated. CS exposure reduced lung SATB1 in a mouse model of COPD, whereas Ant-21 treatment restored SATB1 and reduced S100A9 expression and NF-κB activity. The beneficial effects of Ant-21 in mice were reversed by treatment with SATB1-targeting small interfering RNA. We have identified a pathogenic role for a miR-21/SATB1/S100A9/NF-κB axis in COPD and defined miR-21 as a therapeutic target for this disease.
- Published
- 2021
3. Bacterial load and inflammatory response in sputum of alpha-1 antitrypsin deficiency patients with COPD
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Fabio Lm Ricciardolo, Gaetano Caramori, Davide Vallese, Lorena Delle Donne, Ilaria Ferrarotti, Francesco Cappello, Angelo Corsico, Mauro Carone, Bruno Balbi, Elena Paracchini, Paola Brun, Ian M. Adcock, Isabella Gnemmi, Antonino Di Stefano, Paolo Baderna, Luciano Corda, Sharon Mumby, Claudia Sangiorgi, and Paolo Ruggeri
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medicine.medical_specialty ,COPD ,Alpha 1-antitrypsin deficiency ,business.industry ,CCL3 ,Inflammation ,General Medicine ,medicine.disease ,Gastroenterology ,respiratory tract diseases ,DLCO ,Internal medicine ,medicine ,Sputum ,Interleukin 8 ,medicine.symptom ,business ,Airway - Abstract
Background Airway inflammation may drive the progression of chronic obstructive pulmonary disease (COPD) associated with alpha-1 antitrypsin deficiency (AATD), but the relationship between airway microbiota and inflammation has not been investigated. Methods We studied 21 non-treated AATD (AATD-noT) patients, 20 AATD-COPD patients under augmentation therapy (AATD-AT), 20 cigarette smoke-associated COPD patients, 20 control healthy smokers (CS) and 21 non-smokers (CON) with normal lung function. We quantified sputum inflammatory cells and inflammatory markers (IL-27, CCL3, CCL5, CXCL8, LTB4, MPO) by ELISA, total bacterial load (16S) and pathogenic bacteria by qRT-PCR. Results AATD-AT patients were younger but had similar spirometric and DLCO values compared to cigarette smoke-associated COPD, despite a lower burden of smoking history. Compared to cigarette smoke-associated COPD, AATD-noT and AATD-AT patients had lower sputum neutrophil levels (p=0.0446, p=0.0135), total bacterial load (16S) (p=0.0081, p=0.0223), M. catarrhalis (p=0.0115, p=0.0127) and S. pneumoniae (p=0.0013, p=0.0001). Sputum IL-27 was significantly elevated in CS and cigarette smoke-associated COPD. AATD-AT, but not AATD-noT patients, had IL-27 sputum levels (pg/ml) significantly lower than COPD (p=0.0297) and these positively correlated with FEV1% predicted values (r=0.578, p=0.0307). Conclusions Compared to cigarette smoke-associated COPD, AATD-AT (COPD) patients have a distinct airway inflammatory and microbiological profile. The decreased sputum bacterial load and IL-27 levels in AATD-AT patients suggests that augmentation therapy play a role in these changes.
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- 2019
4. Exaggerated in vivo IL-17 responses discriminate recall responses in active TB
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Mahdad Noursadeghi, Ayesha Khan, Carolin T. Turner, Luis Felipe Peralta, Gabriele Pollara, Ayse U. Akarca, Gillian S. Tomlinson, Cesar Ugarte-Gil, Fabio Lm Ricciardolo, Cristina Venturini, Anna Folino, David Moore, Tina Baker, Lucy C K Bell, Teresa Marafioti, and Benjamin M. Chain
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0303 health sciences ,Tuberculosis ,biology ,business.industry ,Tuberculin ,medicine.disease ,biology.organism_classification ,3. Good health ,Pathogenesis ,Mycobacterium tuberculosis ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunopathology ,Immunology ,medicine ,Interleukin 17 ,business ,Pathogen ,030304 developmental biology ,030215 immunology - Abstract
Background: Host immune responses at the site of Mycobacterium tuberculosis (Mtb) infection serve to contain the pathogen, but also mediate the pathogenesis of tuberculosis (TB) and onward transmission of infection. Based on the premise that active TB disease is predominantly a manifestation of immunopathology, we tested the hypothesis that immune responses at the site of host-pathogen interactions would reveal enrichment of immunopathologic responses in patients with active TB that were absent in individuals with equivalent immune memory for Mtb but without disease. Methods: In cohorts of patients with active TB and cured or latent infection, we undertook molecular profiling at the site of a tuberculin skin test to model in vivo host-pathogen interactions in Mtb infection. Genome-wide transcriptional differences were identified by differential gene expression analyses. Enrichment of immune cells and cytokine activity was derived using specific transcriptional modules. Findings were validated in independent cohorts of patients with active TB, as well as Mtb infected tissues. Results: Active TB in humans is associated with exaggerated IL-17A/F expression, accumulation of Th17 cells and IL-17A bioactivity, including increased neutrophil recruitment and matrix metalloproteinase-1 expression directly implicated in TB pathogenesis. These features discriminate recall responses in patients with active TB from those with cured or latent infection, and are also evident at the site of TB disease. Conclusions: Our data are consistent with a model in which elevated Th17 responses within tissues drive immunopathology and transmission in active TB, and support targeting of the IL-17A/F pathway in host-directed therapy for active TB.
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- 2019
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5. Nitrosative stress in the bronchial mucosa of severe chronic obstructive pulmonary disease
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Alberto Papi, I.M. Adcock, A. Di Stefano, A. Capelli, Paola Brun, Kazuhiro Ito, Antonella Rossi, Gaetano Caramori, Giovanni Abatangelo, K.F. Chung, Claudio F. Donner, P. J. Barnes, and Fabio Lm Ricciardolo
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Male ,Vital Capacity ,Nitric Oxide Synthase Type II ,Cell Count ,medicine.disease_cause ,Epithelium ,Pathogenesis ,Pulmonary Disease, Chronic Obstructive ,chemistry.chemical_compound ,Enos ,Forced Expiratory Volume ,Immunology and Allergy ,COPD ,biology ,medicine.diagnostic_test ,Nitrotyrosine ,Smoking ,Middle Aged ,respiratory system ,Immunohistochemistry ,Reactive Nitrogen Species ,Myeloperoxidase ,Female ,Pulmonary and Respiratory Medicine ,Xanthine Oxidase ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Immunology ,Bronchi ,Respiratory Mucosa ,Bronchial biopsies ,Pathology ,Nitric oxide ,Internal medicine ,medicine ,Humans ,Bronchitis ,Bronchial biopsies, pathology, COPD ,Reactive nitrogen species ,Aged ,Peroxidase ,business.industry ,medicine.disease ,biology.organism_classification ,bronchial biopsies ,respiratory tract diseases ,Oxidative Stress ,pathology ,Bronchoalveolar lavage ,Endocrinology ,chemistry ,Case-Control Studies ,biology.protein ,Tyrosine ,business ,Oxidative stress - Abstract
Background Reactive nitrogen species, formed via the reaction of nitric oxide (NO) with superoxide anion and via (myelo)peroxidase-dependent oxidation of NO(2)(-), have potent proinflammatory and oxidizing actions. Reactive nitrogen species formation and nitrosative stress are potentially involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Objectives To investigate the expression of markers of nitrosative stress, including nitrotyrosine (NT), inducible NO synthase (iNOS), endothelial NO synthase (eNOS), myeloperoxidase (MPO), and xanthine oxidase (XO) in bronchial biopsies and bronchoalveolar lavage from patients with mild to severe stable COPD compared with control groups (smokers with normal lung function and nonsmokers). Methods The expression of NT, iNOS, eNOS, MPO and XO in the bronchial mucosa and bronchoalveolar lavage of patients was measured by using immunohistochemistry, Western blotting, and ELISA and correlated with the inflammatory cell profile. Results Patients with severe COPD in stable phase had higher numbers of NT(+) and MPO(+) cells in their bronchial submucosa compared with mild/moderate COPD, smokers with normal lung function, and nonsmokers ( P 0.01 ). iNOS(+) and eNOS(+) but not XO(+) cells were significantly increased in smokers with COPD or normal lung function compared with nonsmokers ( P 0.05 and P 0.01 , respectively). In patients with COPD, the number of MPO(+) cells was significantly correlated with the number of neutrophils ( r = + 0.61 ; P 0.0025 ) in the bronchial submucosa. Furthermore, the number of NT(+) and MPO(+) cells was negatively correlated with postbronchodilator FEV 1 . Conclusion These data suggest that nitrosative stress, mainly mediated by MPO and neutrophilic inflammation, may contribute to the pathogenesis of severe COPD.
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- 2005
6. Laryngeal spasm mimicking asthma and vitamin d deficiency
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Caterina Bucca, Monica Masoero, Giovanni Rolla, Michela Bellocchia, Fabio Lm Ricciardolo, and Antonio Ciuffreda
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Pulmonary and Respiratory Medicine ,Spirometry ,medicine.medical_specialty ,Laryngeal spasm ,vitamin D deficiency ,Immunology ,Case Report ,Gastroenterology ,calcium deficiency ,Hypocapnia ,Internal medicine ,Hyperventilation ,Vitamin D and neurology ,Immunology and Allergy ,Medicine ,Laryngospasm ,Carnitine ,Myopathy ,medicine.diagnostic_test ,business.industry ,asthma ,medicine.disease ,Surgery ,medicine.symptom ,business ,medicine.drug - Abstract
We present a woman with heterozygous carnitine palmitoyl transferase 2 (CPT-2) deficiency who in the last 6 months suffered from episodic dyspnea and choking. Symptoms could not be attributed to her muscular energy defect, since heterozygous CPT-2 deficiency is usually asymptomatic or causes only mild muscle fatigability. Myopathy is usually triggered by concurrent factors, either genetic (additional muscle enzymes defects) or acquired (metabolic stress). The patient was referred to our respiratory clinic for suspect bronchial asthma. Spirometry showed mild decrease in inspiratory flows. Methacholine challenge was negative. Dyspnea was triggered by hyperventilation-induced hypocapnia, which produced marked decrease in airflow rates, particularly in inspiratory flows, consistent with laryngospasm. Nutritional assessment of the patient showed low serum level of calcium and vitamin D, attributable to avoidance of milk and dairy products for lactose intolerance and to insufficient sunlight exposure. After calcium and vitamin D supplementation episodic laryngospasm disappeared and hypocapnic hyperventilation test induced very mild change in airflow rates. Calcium and vitamin D deficiency may favour laryngeal spasm mimicking asthma, particularly in subjects with underlying myopathy.
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- 2014
7. Randomised double-blind placebo-controlled study of the effect of inhibition of nitric oxide synthesis in bradykinin-induced asthma
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Giuseppe Di Maria, Maria Sapienza, Jay A. Nadel, Fabio Lm Ricciardolo, Pierangelo Geppetti, S. Bellofiore, and Antonino Mistretta
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Adult ,Male ,Bradykinin ,Pharmacology ,Placebo ,Arginine ,Bronchial Provocation Tests ,Bronchospasm ,chemistry.chemical_compound ,Double-Blind Method ,medicine ,Humans ,Enzyme Inhibitors ,Methacholine Chloride ,Asthma ,Aerosols ,Cross-Over Studies ,omega-N-Methylarginine ,Inhalation ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,respiratory tract diseases ,chemistry ,Anesthesia ,Omega-N-Methylarginine ,Methacholine ,Bronchoconstriction ,Female ,medicine.symptom ,Nitric Oxide Synthase ,business ,Lung Volume Measurements ,medicine.drug - Abstract
Bronchoconstriction induced by bradykinin is reduced by the release of nitric oxide (NO) in the airways of guinea pigs. Inhaled NO is known to cause bronchodilatation in asthmatic patients. To find out the role of endogenous NO in airway response to bradykinin in asthma, we examined the effect of the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on broncho-constriction after bradykinin challenge in ten patients with mild asthma.The study had a randomised, double-blind, placebo-controlled, cross-over design. Participants were studied during two phases, each consisting of 2 study days. After baseline measurements of forced expiratory volume in 1 s (FEV1) participants inhaled an aerosol of L-NMMA or saline (placebo). After 5 min, saline and doubling doses of bradykinin (from 0.25 nmol) were inhaled until FEV1 fell by at least 20% of the post-saline value. The effect of L-NMMA and placebo on airway response to doubling concentrations of methacholine (from 0.03 mg/mL) was then examined. We also assessed the effect of the inactive enantiomer of L-NMMA, D-NMMA, and placebo on bronchoconstriction after bradykinin or methacholine challenge in six of the participants.The geometric mean of the provocative dose producing a 20% fall in FEV1 to bradykinin was 138.0 nmol (range 48.2-475.2 nmol) after placebo and 11.2 nmol (range 0.9-51.3 nmol) after L-NMMA (p0.01). L-NMMA also caused a decrease in the provocative concentration of methacholine producing a 20% fall in FEV1 from 0.93 mg/mL (range 0.12-2.55 mg/mL) to 0.38 mg/mL (range 0.06-0.92 mg/mL; p0.01). In contrast, D-NMMA did not affect airway response to bradykinin or methacholine.The results suggest that bronchoconstriction after bradykinin inhalation is greatly inhibited by the formation of NO in airways of asthmatic patients and that NO could have a bronchoprotective role in asthma.
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- 1996
8. Nitric oxide and response to inhaled bradykinin in severe asthma
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Peter J. Sterk, Pierangelo Geppetti, Fabio Lm Ricciardolo, Giuseppe Di Maria, and Antonino Mistretta
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chemistry.chemical_compound ,chemistry ,business.industry ,Severe asthma ,Bradykinin ,Medicine ,General Medicine ,Pharmacology ,business ,Nitric oxide - Published
- 1998
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