75 results on '"Vulcano, M."'
Search Results
2. Catalogue of the Canthonini (Col. Scarab.) Inhabiting the Western Hemisphere
- Author
-
Vulcano, M A, Pereira, Francisco Silvério, and BioStor
- Published
- 1964
3. P.183 A neuroimaging study of functional connectivity during an emotion regulation task in major depressive disorder and borderline personality disorder
- Author
-
Arteaga, V. De La Peña, primary, Steward, T., additional, Berruga-Sánchez, M., additional, Goldberg, X., additional, Martínez-Zalacaín, I., additional, Wainsztein, A., additional, Mercé, R. Álvarez, additional, Camacho, V., additional, Vulcano, M., additional, Abulafia, C., additional, Vigo, D., additional, Villarreal, M., additional, Cardoner, N., additional, Nemeroff, C., additional, Castro, M.N., additional, Menchón, J.M., additional, Guinjoan, S., additional, and Soriano-Mas, C., additional
- Published
- 2019
- Full Text
- View/download PDF
4. Unique regulation of CCL18 production by maturating dendritic cells: 216
- Author
-
Vulcano, M., Struyf, S., Scapini, P., Cassatella, M., Riboldi, E., Mantovani, A., Van Damme, J., and Sozzani, S.
- Published
- 2003
5. Production of oxygen radicals in phatogen-activated dendritic cells: 155
- Author
-
Riboldi, E., Vulcano, M., Lissandrini, D., Mazzi, P., Dusi, S., and Sozzani, S.
- Published
- 2003
6. Different recognition and scavenging of native and truncated CCL22 by the chemokine receptor D6: 152
- Author
-
Bonecchi, R., Locati, M., Vulcano, M., Sironi, M., Fra, A., Gobbi, M., Vecchi, A., Sozzani, S., and Mantovani, A.
- Published
- 2003
7. Interleukin-1β induces in vivo tolerance to lipopolysaccharide in mice
- Author
-
ALVES-ROSA, F, VULCANO, M, BEIGIER-BOMPADRE, M, FERNÁNDEZ, G, PALERMO, M, and ISTURIZ, M. A
- Published
- 2002
8. N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibits tumour necrosis factor-alpha (TNF-α) production on lipopolysaccharide(LPS)-stimulated human neutrophils
- Author
-
VULCANO, M., ALVES ROSA, M. F., MINNUCCI, F. S., CHERÑAVSKY, A. C., and ISTURIZ, M. A.
- Published
- 1998
9. L-arginine/nitric oxide pathway activation in platelets of migraine patients with and without aura
- Author
-
Gallai, V., Floridi, A., Mazzotta, G., Codini, M., Tognoloni, M., Vulcano, M. R., Sartori, M., Russo, S., Alberti, A., Michele, F., and Sarchielli, P.
- Published
- 1996
10. Anti-Oxidants Inhibit the Enhancement of the Immune Response Caused by Oil Adjuvants
- Author
-
Di Gianni, P., Minnucci, F. S., Alves Rosa, M. F., Vulcano, M., and Isturiz, M. A.
- Published
- 1996
11. CD40 activation of BCP-ALL cells generates 11L-10-producing, 11L-12-defective APCs that induce allogeneic T-cell anergy
- Author
-
D'Amico, G, Vulcano, M, Bugarin, C, Bianchi, G, Pirovano, G, Bonamino, M, Marin, V, Allavena, P, BIAGI, ETTORE, BIONDI, ANDREA, D'Amico, G, Vulcano, M, Bugarin, C, Bianchi, G, Pirovano, G, Bonamino, M, Marin, V, Allavena, P, Biagi, E, and Biondi, A
- Subjects
CD40L, leukemia, APC - Abstract
The use of leukemia cells as antigen-presenting cells (APCs) in immunotherapy is critically dependent on their capacity to initiate and sustain an antitumor-specific immune response. Previous studies suggested that pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells could be manipulated in vitro through the CD40-CD40L pathway to increase their immunostimulatory capacity. We extended the APC characterization of CD40L-activated BCP-ALL for their potential use in immunotherapy in a series of 19 patients. Engaging CD40 induced the up-regulation of CCR7 in 7 of 11 patients and then the migration to CCL19 in 2 of 5 patients. As accessory cells, CD40L-activated BCP-ALL induced a strong proliferation response of naive T lymphocytes. Leukemia cells, however, were unable to sustain proliferation over time, and T cells eventually became anergic. After CD40-activation, BCP-ALL cells released substantial amounts of interieukin-1 0 (IL-10) but were unable to produce bioactive IL-12 or to polarize T(H)1 effectors. Interestingly, adding exogenous IL-12 induced the generation of interferon-gamma (IFN-gamma)-secreting T(H)1 effectors and reverted the anergic profile in a secondary response. Therefore, engaging CD40 on BCP-ALL cells is insufficient for the acquisition of full functional properties of immunostimulatory APCs. These results suggest caution against the potential use of CD40L-activated BCP-ALL cells as agents for immunotherapy unless additional stimuli, such as IL-12, are provided.
- Published
- 2004
12. Unique regulation of CCL18 production by maturing dendritic cells
- Author
-
Vulcano, M, Struyf, Scapini, Patrizia, Cassatella, Marco Antonio, Bernasconi, P, Bonecchi, R, Calleri, A, Penna, G, Adorini, L, Mantovani, A, VAN DAMME, J, and Sozzani, S.
- Published
- 2003
13. Production of oxygen radicals in pathogen-activated dendritic cells
- Author
-
Riboldi, E, Vulcano, M, Lissandrini, Daniele, Mazzi, Paola, Dusi, Stefano, and Sozzani, S.
- Subjects
NADPH oxidase ,Dendritic Cells ,Toll-like Receptors - Published
- 2003
14. Denditic cells as a major source of macrophage derived chemokine/Cin vito and in vivo
- Author
-
Vulcano, M., Albanesi, C., Stoppacciaro, Antonella, Bagnati, R., D'Amico, G, Struyf, S., Transdico, P., Bonecchi, R., DEL PRETE, A., Allavena, P., Ruco, Luigi, Chiabrando, C., and Sozzani, Silvano
- Published
- 2001
15. Divergent regulation of MIP-3alpha/CCL20 and PARC/DC-CK1/CCL18 during dendritic cell maturation
- Author
-
Vulcano, M., Scapini, Patrizia, Struyf, S., Cassatella, Marco Antonio, Bernasconi, S., Bonecchi, R., Mantovani, A., Vandamme, J., and Sozzani, S.
- Subjects
dendritic cells ,chemokines ,CCL20 ,CCL18 - Published
- 2001
16. The earliest known fossil ant (first southern hemisphere Mesozoic record) (Hymenoptera: Formicidae: Myrmeciinae)
- Author
-
Brandão, C. R. F., Martins-Neto, R. G., Vulcano, M. A., Cora, Joe, and Johnson, Norm
- Subjects
taxonomy ,Ampulicidae ,Arthropoda ,Hexapoda ,Animalia ,insects ,Apoidea ,Hymenoptera ,biodiversity - Abstract
xBio:D Automated Upload
- Published
- 1990
- Full Text
- View/download PDF
17. Interleukin-1β inducesin vivotolerance to lipopolysaccharide in mice
- Author
-
ALVES-ROSA, F, primary, VULCANO, M, additional, BEIGIER-BOMPADRE, M, additional, FERNÁNDEZ, G, additional, PALERMO, M, additional, and ISTURIZ, M A, additional
- Published
- 2002
- Full Text
- View/download PDF
18. N-formyl-methionyl-leucyl-phenylalanine (fMLP) inhibits tumour necrosis factor-alpha (TNF-α) production on lipopolysaccharide (LPS)-stimulated human neutrophils
- Author
-
Vulcano, M, primary, Rosa, M F Alves, additional, Minnucci, F S, additional, Cherñavsky, A C, additional, and Isturiz, M A, additional
- Published
- 1998
- Full Text
- View/download PDF
19. Anti‐Oxidants Inhibit the Enhancement of the Immune Response Caused by Oil Adjuvants
- Author
-
GIANNI, P. DI, primary, MINNUCCI, F. S., additional, ALVES ROSA, M. F., additional, VULCANO, M., additional, and ISTURIZ, M. A., additional
- Published
- 1996
- Full Text
- View/download PDF
20. THE EARLIEST KNOWN FOSSIL ANT (FIRST SOUTHERN HEMISPHERE MESOZOIC RECORD) (HYMENOPTERA: FORMICIDAE: MYRMECIINAE).
- Author
-
BRANDÃO, CARLOS ROBERTO F., MARTINS-NETO, RAFAEL G., and VULCANO, M. APARECIDA
- Published
- 1989
21. The down-regulation of FcγRII and FcγRIIIB by N-formyl-methionyl-leucyl-phenylalanine (FMLP) depends on secretory events in human neutrophils
- Author
-
Alves-Rosa, M.F, Vulcano, M, Beigier, M, Breyer, I, and Isturiz, M.A
- Published
- 1999
- Full Text
- View/download PDF
22. Diatoms assemblages in headwaters influenced by glaciers and permafrost under alpine deglaciation
- Author
-
Vulcano, M. C., Brighenti, S., Bruno, M. C., leonardo cerasino, Tirler, W., and Monica Tolotti
- Subjects
Alpine streams ,Diatoms ,Rock glaciers ,Settore BIO/07 - ECOLOGIA ,Climate change ,Glacier
23. Unique regulation of CCL18 production by maturing dendritic cells
- Author
-
Vulcano, M., Struyf, S., Scapini, P., Cassatella, M., Bernasconi, S., Bonecchi, R., Calleri, A., Penna, G., Adorini, L., Luini, W., Mantovani, A., Damme, J., and Silvano Sozzani
24. Duas novas espécies do gênero Scatonomus Er. 1835 (Col. scarabaeidae)
- Author
-
Vulcano, M. Aparecida, primary and Pereira, F. S., additional
- Published
- 1973
- Full Text
- View/download PDF
25. The Earliest Known Fossil Ant (First Southern Hemisphere Mesozoic Record) (Hymenoptera: Formicidae: Myrmeciinae)
- Author
-
Roberto F. Brandão, Carlos, G. Martins-Neto, Rafael, and Aparecida Vulcano, M.
- Published
- 1989
- Full Text
- View/download PDF
26. Inhibition of normal natural killer cytotoxicity by sera from hemophilic patients
- Author
-
Vulcano, M., Olabuenaga, S. E., Galassi, N., and Felippo, M.
- Published
- 1993
- Full Text
- View/download PDF
27. Variations in the platelet arginine/nitric oxide pathway during the ovarian cycle in females affected by menstrual migraine.
- Author
-
Sarchielli, P, Tognoloni, M, Russo, S, Vulcano, MR, Feleppa, M, Malà, M, Sartori, M, Gallai, V, Vulcano, M R, and Malà, M
- Subjects
- *
MIGRAINE , *MENSTRUATION disorders , *ARGININE , *NITRIC oxide , *ARGININE metabolism , *ANALYSIS of variance , *BLOOD platelets , *BLOOD platelet aggregation , *COLLAGEN , *MENSTRUAL cycle , *NUCLEOTIDES - Abstract
Previous studies have reported the existence of an arginine/nitric oxide (NO) pathway and the involvement of a Ca2+, NADPH-dependent nitric oxide synthase enzyme (NOS) in the generation of NO in human platelets. In the present research, we determined the rate of production of NO and cGMP in the cytosol of platelets stimulated by collagen in 20 females with menstrual migraine (MM), (age range 24-40 years), assessed in the follicular and luteal phases, interictally and ictally in the latter period. The same patients were also assessed at mid-cycle. At the same time, the variations in the collagen response of platelets were evaluated. Moreover, these parameters were determined in the same periods in 20 age-matched control females and in 20 females affected by non-menstrually related migraine (nMM). The collagen-stimulated production of NO in the cytosol of the platelet cytosol was significantly higher in migraine patients with MM than in the control subjects. In MM patients, the increase was greater in the luteal phase of the cycle than during the follicular phase (p < 0.005). A rise in NO production in platelets was also present, although to a lesser extent, in females affected by nMM compared to the healthy females, but this rise was most evident at ovulation (p < 0.001). A slight but significant increase was also observed at mid-cycle in control women, but this increase did not reach the values determined in the migraine groups (p < 0.02). NO production in platelets stimulated by collagen was significantly increased during attacks with respect to the interictal period in both patient groups. Similar variations were observed in the production of cGMP in MM and nMM patients. The increase in NO production was accompanied by a decrease in platelet aggregation in the migraine groups compared with the control group; this decrease was most evident at mid-cycle in nMM patients and in the luteal phase in MM patients. These data suggest an activation of the L-arginine/ NO pathway in MM and nMM patients which could explain the modifications in the platelet response to collagen evidenced in migraine-free periods and during attacks. The activation of this pathway is more accentuated in the luteal phase in MM patients, and this could be the cause of the increased susceptibility to migraine attacks in perimenstrual and menstrual periods in these patients. [ABSTRACT FROM AUTHOR]
- Published
- 1996
- Full Text
- View/download PDF
28. The protein C pathway in inflammatory bowel disease: the missing link between inflammation and coagulation
- Author
-
Mark Lust, Marisa Vulcano, Silvio Danese, Lust, M, Vulcano, M, and Danese, S
- Subjects
Endothelium ,Regulator ,Inflammation ,Thrombomodulin ,Inflammatory bowel disease ,medicine ,Animals ,Humans ,Colitis ,Intestinal Mucosa ,Molecular Biology ,Blood Coagulation ,business.industry ,medicine.disease ,Inflammatory Bowel Diseases ,medicine.anatomical_structure ,Immunology ,Molecular Medicine ,Endothelium, Vascular ,medicine.symptom ,Signal transduction ,business ,Protein C ,medicine.drug ,Signal Transduction - Abstract
Traditionally described as a major anti-coagulant system, the protein C (PC) pathway, consisting of thrombomodulin, the endothelial cell protein C receptor and activated PC (APC), is gaining increasing attention as an important regulator of microvascular inflammation. Although they possess several anti-inflammatory and cytoprotective functions, the expression and function of the components of the PC pathway is downregulated during inflammation. Recent evidence suggests that the PC pathway is defective in patients with inflammatory bowel disease (IBD) and that restoring its function has anti-inflammatory effects on cultured intestinal microvascular endothelial cells and in animal models of colitis. Here, we propose that the PC pathway has an important role in governing intestinal microvascular inflammation and might provide a novel therapeutic target in the management of IBD.
- Published
- 2007
29. Intestinal epithelial cells control dendritic cell function
- Author
-
Maria Rescigno, Marcello Chieppa, Monica Rimoldi, Marisa Vulcano, Paola Allavena, Rimoldi, M., Chieppa, M., Vulcano, M., Allavena, P., and Rescigno, M.
- Subjects
Salmonella typhimurium ,Chemokine ,Dendritic Cell ,Bacterial Infection ,General Biochemistry, Genetics and Molecular Biology ,Proinflammatory cytokine ,Tight Junctions ,Mucosa ,Interleukin 22 ,Mice ,History and Philosophy of Science ,Animals ,Humans ,Bacillus subtili ,Intestinal Mucosa ,Coculture Technique ,Cytokine ,Tight junction ,Epithelial polarity ,A549 cell ,Bacteria ,biology ,Follicular dendritic cells ,Animal ,General Neuroscience ,JAM ,Dendritic cell ,Bacterial Infections ,Dendritic Cells ,Coculture Techniques ,Intestine ,Cell biology ,Epithelial cell ,biology.protein ,Cytokines ,Chemokines ,Human ,Bacillus subtilis ,Lactobacillus plantarum - Abstract
Dendritic cells (DCs) comprise a family of cells specializing in antigen capture and presentation to T cells. We have recently shown that DC play an active role in bacterial uptake across mucosal surfaces. Indeed, DC are able to open tight junctions and to sample antigens directly across epithelia, both in vitro and in vivo. Because DC express tight junction proteins, the integrity of the epithelial barrier is preserved. In this study we have analyzed the possible involvement of epithelial cells in controlling DC function. We developed an in vitro model in our laboratory consisting of a three-player system of dendritic cells, epithelial cell monolayers, and bacteria. The crosstalk between epithelial cells and dendritic cells was analyzed, and epithelial cells were tested for their capacity to release cytokines and chemokines that induce the migration and activation of DC. We show that the capacity of epithelial eels to produce cytokines and activate DC is dependent on the invasiveness of the bacteria tested. In particular, invasive bacteria stimulate epithelial cells to release proinflammatory cytokines and to induce the maturation state of DC. By contrast, noninvasive bacteria are unable to stimulate epithelial cells, but can activate DC directly when DC translocate to the apical side. In conclusion, epithelial cells are not simply a barrier to bacteria entering via the oral route, but actively influence the activating properties of bystander DC. © 2004 New York Academy of Sciences.
- Published
- 2005
30. Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different
- Author
-
Monica Rimoldi, Marcello Chieppa, Maria Rescigno, Paola Allavena, Marisa Vulcano, Paola Larghi, Rimoldi, M., Chieppa, M., Larghi, P., Vulcano, M., Allavena, P., and Rescigno, M.
- Subjects
Chemokine ,Th2 response ,Immunology ,Flagellum ,Dendritic Cell ,Gram-Positive Bacteria ,Monocyte ,Biochemistry ,Monocytes ,Proinflammatory cytokine ,Mice ,Th2 Cells ,Animals ,Humans ,Th2 Cell ,Cells, Cultured ,Epithelial Cell ,Chemokine CCL20 ,Tight junction ,biology ,Monocyte derived ,Animal ,Epithelial Cells ,Cell Differentiation ,Dendritic Cells ,Cell Biology ,Hematology ,Macrophage Inflammatory Proteins ,Th1 Cells ,biology.organism_classification ,Interleukin-12 ,Cell biology ,Interleukin-10 ,Th1 Cell ,Flagella ,Macrophage Inflammatory Protein ,Chemokines, CC ,biology.protein ,Function (biology) ,Bacteria ,Human - Abstract
Dendritic cells (DCs) are able to open the tight junctions between adjacent epithelial cells (ECs) and to take up both invasive and noninvasive bacteria directly from the intestinal lumen. In this study, we describe a tight cross talk between ECs and human monocyte-derived DCs (MoDCs) in bacterial handling across epithelial monolayers. We show that the release of proinflammatory mediators by ECs in response to bacteria is dependent on bacterial invasiveness and on the presence of flagella. This correlates with the capacity of EC-derived factors to modulate MoDC function. MoDCs incubated with supernatants of bacteria-treated ECs are “noninflammatory” as they release interleukin-10 (IL-10) but not IL-12 and can drive only T helper (Th)-2 type T cells. Moreover, noninflammatory MoDCs release chemokines aimed at recruiting Th2 and T-regulatory cells. In contrast, when MoDCs are incubated with ECs and bacteria in a transwell coculture system, and can contact directly the bacteria across stimulated EC monolayers, they are more inflammatory as they release IL-12 and IL-10 and induce both Th1 and Th2 responses. These results suggest that ECs are not simply a barrier to bacteria entering via the oral route, but they actively influence the activating properties of DCs. (Blood. 2005;106:2818-2826)
- Published
- 2005
31. Childhood adversity modulation of central autonomic network components during cognitive regulation of emotion in major depressive disorder and borderline personality disorder.
- Author
-
Wainsztein AE, Castro MN, Goldberg X, Camacho-Téllez V, Vulcano M, Abulafia C, Ladrón-de-Guevara S, Cardoner N, Nemeroff CB, Menchón JM, Soriano-Mas C, Villarreal MF, and Guinjoan SM
- Subjects
- Cognition, Emotions physiology, Humans, Adverse Childhood Experiences, Borderline Personality Disorder psychology, Depressive Disorder, Major diagnostic imaging
- Abstract
Adverse childhood experiences (ACEs) have lifelong effects on emotional behavior and are frequent in Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD). The Central Autonomic Network (CAN), which modulates heart rate variability (HRV), comprises brain regions that mediate emotion regulation processes. However, it remains unclear the effect of ACEs on CAN dynamics and its relationship with HRV in these disorders. We studied the effects of ACEs on the brain and HRV simultaneously, during regulation of psychological stress in 19 BPD, 20 MDD and 20 healthy controls (HC). Participants underwent a cognitive reappraisal task during fMRI with simultaneous ECG acquisition. ACEs exposure was associated with increased activity of CAN and salience network components in patients with MDD compared to BPD during cognitive reappraisal. A brain-autonomic coupling was found in BPD relative to HC during emotion regulation, whereby greater activity of left anterior cingulate and medial superior frontal gyrus areas was coupled with increased HRV. Results suggest that ACEs exposure is associated with a distinct activation of the CAN and salience network regions governing responses to psychological stress in MDD compared to BPD. These alterations may constitute a distinctive neurobiological mechanism for abnormal emotion processing and regulation related to ACEs in MDD., (Copyright © 2021. Published by Elsevier B.V.)
- Published
- 2021
- Full Text
- View/download PDF
32. Blocking TH17-polarizing cytokines by histone deacetylase inhibitors in vitro and in vivo.
- Author
-
Bosisio D, Vulcano M, Del Prete A, Sironi M, Salvi V, Salogni L, Riboldi E, Leoni F, Dinarello CA, Girolomoni G, and Sozzani S
- Subjects
- Animals, Cells, Cultured, Chemokines genetics, Chemokines metabolism, Cytokines antagonists & inhibitors, Cytokines metabolism, Dendritic Cells drug effects, Dendritic Cells metabolism, Enzyme-Linked Immunosorbent Assay, Female, Histone Deacetylases metabolism, Humans, Hydroxamic Acids pharmacology, In Vitro Techniques, Interferon-gamma metabolism, Interleukin-12 antagonists & inhibitors, Interleukin-23 antagonists & inhibitors, Lipopolysaccharides pharmacology, Mice, Mice, Inbred C57BL, Monocytes cytology, Monocytes drug effects, Monocytes metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Receptors, Interferon metabolism, Reverse Transcriptase Polymerase Chain Reaction, Vorinostat, Interferon gamma Receptor, Enzyme Inhibitors pharmacology, Histone Deacetylase Inhibitors, Interleukin-12 metabolism, Interleukin-23 metabolism, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Histone deacetylase (HDAC) inhibitors are small molecules inducing cell-cycle arrest, differentiation, and apoptosis, currently undergoing clinical trials as anticancer drugs. In addition, emerging evidence suggests HDAC inhibitors may have anti-inflammatory and immunomodulatory properties as well, although the molecular mechanisms remain poorly defined. Given the central role of dendritic cells (DC) in the induction and maintenance of the inflammatory and immune response, we investigated the effects of HDAC inhibitors on the maturation and activation of human monocyte-derived DC in the presence of LPS and IFN-gamma. Our results show that the production of T(H)1- and T(H)17-inducing cytokines, namely IL-12 and IL-23, was inhibited by trichostatin A (72% and 52%, respectively) and suberoylanilide hydroxamic acid (86% and 83%). Strikingly, HDAC inhibitors were effective if added simultaneously as well as after the proinflammatory challenge, and their effect was not associated to a reduction of expression or function of LPS/IFN-gamma receptors. These findings were confirmed in two different murine models. In addition, HDAC inhibitors selectively blocked the production of T(H)1-attracting chemokines CXCL9, CXCL10, and CXCL11. The reduction of T(H)1- and T(H)17-inducing cytokines as well as T(H)1-attracting chemokines may represent relevant mechanisms through which HDAC inhibitors at nonproapoptotic doses exert their immunomodulatory properties.
- Published
- 2008
- Full Text
- View/download PDF
33. The protein C pathway in inflammatory bowel disease: the missing link between inflammation and coagulation.
- Author
-
Lust M, Vulcano M, and Danese S
- Subjects
- Animals, Blood Coagulation, Endothelium, Vascular immunology, Endothelium, Vascular metabolism, Humans, Inflammation, Inflammatory Bowel Diseases immunology, Intestinal Mucosa immunology, Intestinal Mucosa metabolism, Inflammatory Bowel Diseases metabolism, Protein C metabolism, Signal Transduction
- Abstract
Traditionally described as a major anti-coagulant system, the protein C (PC) pathway, consisting of thrombomodulin, the endothelial cell protein C receptor and activated PC (APC), is gaining increasing attention as an important regulator of microvascular inflammation. Although they possess several anti-inflammatory and cytoprotective functions, the expression and function of the components of the PC pathway is downregulated during inflammation. Recent evidence suggests that the PC pathway is defective in patients with inflammatory bowel disease (IBD) and that restoring its function has anti-inflammatory effects on cultured intestinal microvascular endothelial cells and in animal models of colitis. Here, we propose that the PC pathway has an important role in governing intestinal microvascular inflammation and might provide a novel therapeutic target in the management of IBD.
- Published
- 2008
- Full Text
- View/download PDF
34. Anti-inflammatory pretreatment enables an efficient dendritic cell-based immunotherapy against established tumors.
- Author
-
Chiarella P, Vulcano M, Bruzzo J, Vermeulen M, Vanzulli S, Maglioco A, Camerano G, Palacios V, Fernández G, Brando RF, Isturiz MA, Dran GI, Bustuoabad OD, and Ruggiero RA
- Subjects
- Animals, Blotting, Western, Cancer Vaccines therapeutic use, Dendritic Cells immunology, Dexamethasone therapeutic use, Female, Flow Cytometry, Male, Mice, Mice, Inbred BALB C, Neoplasms, Experimental immunology, Anti-Inflammatory Agents therapeutic use, Dendritic Cells transplantation, Immune Tolerance drug effects, Immunotherapy methods, Inflammation drug therapy, Neoplasms, Experimental therapy
- Abstract
Although animals can be immunized against the growth of some tumor implants, most of the attempts to use immunotherapy to cause the regression of animal and human tumors once they have become established have been disappointing even when strongly immunogenic tumors were used as target. In this paper, we demonstrate that the failure to achieve an efficient immunological treatment against an established strongly immunogenic murine fibrosarcoma was paralleled with the emergence of a state of immunological unresponsiveness (immunological eclipse) against tumor antigens observed when the tumor surpassed the critical size of 500 mm(3). In turn, the onset of the immunological eclipse was coincidental with the onset of a systemic inflammatory condition characterized by a high number of circulating and splenic polymorphonucleated neutrophils (PMN) displaying activation and Gr1(+)Mac1(+) phenotype and an increasing serum concentration of the pro-inflammatory cytokines TNF-alpha, IL-1beta and IL-6 cytokines and C-reactive protein (CRP) and serum A amyloid (SAA) phase acute proteins. Treatment of tumor-bearing mice with a single low dose (0.75 mg/kg) of the synthetic corticoid dexamethasone (DX) significantly reduced all the systemic inflammatory parameters and simultaneously reversed the immunological eclipse, as evidenced by the restoration of specific T-cell-dependent concomitant immunity, ability of spleen cells to transfer anti-tumor activity and recovery of T-cell signal transduction molecules. Two other anti-inflammatory treatments by using indomethacin or dimeric TNF-alpha receptor, also partially reversed the immunological eclipse although the effect was not as striking as that observed with DX. The reversion of the immunological eclipse was not enough on its own to inhibit the primary growing tumor. However, when we used the two-step strategy of inoculating DX to reverse the eclipse and then dendritic cells loaded with tumor antigens (DC) as an immunization booster, a significant inhibition of the growth of both established tumors and remnant tumor cells after excision of large established tumors was observed, despite the fact that the vaccination alone (DC) had no effect or even enhanced tumor growth in certain circumstances. The two-step strategy of tumor immunotherapy that we present is based on the rationale that it is necessary to eliminate or ameliorate the immunological eclipse as a precondition to allow an otherwise ineffective anti-tumor immunological therapy to have a chance to be successful.
- Published
- 2008
- Full Text
- View/download PDF
35. Tolerance in intestinal inflammation and cancer.
- Author
-
Vulcano M, Danese S, and Sica A
- Subjects
- Animals, Bacteria immunology, Bacteria pathogenicity, Colitis complications, Colitis microbiology, Colitis pathology, Dendritic Cells immunology, Epithelial Cells immunology, Humans, Interleukin-10 metabolism, Intestinal Mucosa microbiology, Intestinal Mucosa pathology, Intestinal Neoplasms microbiology, Intestinal Neoplasms pathology, Intestines microbiology, Intestines pathology, Lymph Nodes immunology, Macrophages immunology, Peyer's Patches immunology, T-Lymphocytes, Regulatory immunology, Transforming Growth Factor beta metabolism, Tumor Escape, Colitis immunology, Immune Tolerance, Immunity, Mucosal, Intestinal Mucosa immunology, Intestinal Neoplasms immunology, Intestines immunology
- Abstract
In the human body, mucosal surfaces of the intestinal tract are the largest and one of the most complex parts of the immune system. These surfaces are covered by a layer of epithelial cells which allows efficient absorption of nutrients but also serves to separate the intestine from an environment loaded with potential harmful agents. Discrimination between beneficial commensal bacteria, harmless antigens and pathogenic microorganisms is a central issue in the role that gut immune cells play in maintaining the balance between immune response and tolerance. However, the basis of this discrimination in the mucosal immune system, where this occurs and how it can affect both local and systemic responses is not yet well understood. Nevertheless, antigen uptake and presentation seems to be a crucial factor in this issue. In this review, we will discuss the key role of immune intestinal cells in the development of mucosal immunity, tolerance and disease.
- Published
- 2008
- Full Text
- View/download PDF
36. Immune complexes inhibit differentiation, maturation, and function of human monocyte-derived dendritic cells.
- Author
-
Laborde EA, Vanzulli S, Beigier-Bompadre M, Isturiz MA, Ruggiero RA, Fourcade MG, Catalan Pellet AC, Sozzani S, and Vulcano M
- Subjects
- Animals, Antigen-Antibody Complex blood, Autoimmune Diseases immunology, Autoimmune Diseases metabolism, Autoimmune Diseases pathology, Cells, Cultured, Dendritic Cells metabolism, Dendritic Cells pathology, Dose-Response Relationship, Immunologic, Growth Inhibitors blood, Humans, Immunoglobulin G metabolism, Lupus Erythematosus, Systemic immunology, Lupus Erythematosus, Systemic metabolism, Lupus Erythematosus, Systemic pathology, Lymphocyte Activation immunology, Lymphocyte Culture Test, Mixed, Monocytes metabolism, Monocytes pathology, Rabbits, Receptors, IgG antagonists & inhibitors, Receptors, IgG biosynthesis, Receptors, IgG physiology, T-Lymphocytes immunology, Time Factors, Antigen-Antibody Complex physiology, Cell Differentiation immunology, Cell Lineage immunology, Dendritic Cells cytology, Dendritic Cells immunology, Growth Inhibitors physiology, Monocytes cytology, Monocytes immunology
- Abstract
The interaction between immune complexes (IC) and the receptors for the Fc portion of IgG (FcgammaRs) triggers regulatory and effector functions in the immune system. In this study, we investigated the effects of IC on differentiation, maturation, and functions of human monocyte-derived dendritic cells (DC). When IC were added on day 0, DC generated on day 6 (IC-DC) showed lower levels of CD1a and increased expression of CD14, MHC class II, and the macrophage marker CD68, as compared with normally differentiated DC. The use of specific blocking FcgammaR mAbs indicated that the effect of IC was exerted mainly through their interaction with FcgammaRI and to a lesser extend with FcgammaRII. Immature IC-DC also expressed higher levels of CD83, CD86, and CD40 and the expression of these maturation markers was not further regulated by LPS. The apparent lack of maturation following TLR stimulation was associated with a decreased production of IL-12, normal secretion of IL-10 and CCL22, and increased production of CXCL8 and CCL2. IC-DC displayed low endocytic activity and a reduced ability to induce allogeneic T cell proliferation both at basal and LPS-stimulated conditions. Altogether, these data reveal that IC strongly affect DC differentiation and maturation. Skewing of DC function from Ag presentation to a proinflammatory phenotype by IC resembles the state of activation observed in DC obtained from patients with chronic inflammatory autoimmune disorders, such as systemic lupus erythematosus disease and arthritis. Therefore, the altered maturation of DC induced by IC may be involved in the pathogenesis of autoimmune diseases.
- Published
- 2007
- Full Text
- View/download PDF
37. 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells.
- Author
-
Penna G, Amuchastegui S, Giarratana N, Daniel KC, Vulcano M, Sozzani S, and Adorini L
- Subjects
- Active Transport, Cell Nucleus, CD4 Antigens analysis, Chemokine CCL17, Chemokine CCL22, Chemokines, CC metabolism, Dendritic Cells immunology, Gene Expression drug effects, Histocompatibility Antigens Class II genetics, Humans, Immunosuppression Therapy, Ligands, Membrane Glycoproteins, Myeloid Cells immunology, NF-kappa B metabolism, Phosphorylation, Plasma Cells drug effects, Plasma Cells immunology, Receptors, CCR4, Receptors, Calcitriol agonists, Receptors, Cell Surface genetics, Receptors, Chemokine metabolism, Receptors, Immunologic, Th1 Cells drug effects, Th1 Cells immunology, Transcription, Genetic drug effects, Calcitriol pharmacology, Calcitriol physiology, Dendritic Cells drug effects, Immune Tolerance drug effects, Myeloid Cells drug effects
- Abstract
1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is an immunomodulatory agent inducing dendritic cells (DCs) to become tolerogenic. To further understand its mechanisms of action, we have examined the effects of 1,25(OH)(2)D(3) on tolerogenic properties of blood myeloid (M-DCs) and plasmacytoid (P-DCs) human DC subsets. Exposure of M-DCs to 1,25(OH)(2)D(3) up-regulated production of CCL22, a chemokine attracting regulatory T cells, whereas production of CCL17, the other CCR4 ligand, was reduced. 1,25(OH)(2)D(3) also decreased IL-12p75 production by M-DCs, as expected, and inhibited CCR7 expression. 1,25(OH)(2)D(3) treatment markedly increased CD4(+) suppressor T cell activity while decreasing the capacity of M-DCs to induce Th1 cell development. Surprisingly, 1,25(OH)(2)D(3) did not exert any discernible effect on tolerogenic properties of P-DCs, and even their high production of IFN-alpha was not modulated. In particular, the intrinsically high capacity of P-DCs to induce CD4(+) suppressor T cells was unaffected by 1,25(OH)(2)D(3). Both DC subsets expressed similar levels of the vitamin D receptor, and its ligation by 1,25(OH)(2)D(3) similarly activated the primary response gene cyp24. Interestingly, 1,25(OH)(2)D(3) inhibited NF-kappaB p65 phosphorylation and nuclear translocation in M-DCs but not P-DCs, suggesting a mechanism for the inability of 1,25(OH)(2)D(3) to modulate tolerogenic properties in P-DCs.
- Published
- 2007
- Full Text
- View/download PDF
38. [Reversion of the immunological eclipse and therapeutic vaccination against cancer in an experimental model].
- Author
-
Chiarella P, Vulcano M, Laborde E, Vermeulen M, Bruzzo J, Rearte B, Bustuoabad OD, and Ruggiero RA
- Subjects
- Animals, Anti-Inflammatory Agents immunology, Anti-Inflammatory Agents therapeutic use, Cancer Vaccines immunology, Carcinogens, Dexamethasone immunology, Dexamethasone therapeutic use, Disease-Free Survival, Fibrosarcoma chemically induced, Fibrosarcoma immunology, Immune Tolerance drug effects, Inflammation drug therapy, Methylcholanthrene, Mice, Mice, Inbred BALB C, Sarcoma, Experimental chemically induced, Sarcoma, Experimental immunology, Cancer Vaccines therapeutic use, Dendritic Cells immunology, Fibrosarcoma drug therapy, Immune Tolerance immunology, Sarcoma, Experimental drug therapy
- Abstract
Although animals can be prophylactically immunized against the growth of tumor implants, most of the attempts to use immunotherapy to cause the regression of animal and human tumors once they become established have been unsuccessful. To understand the nature of this refractoriness we have studied a methylcholanthrene-induced and strongly immunogenic murine fibrosarcoma. In our model, the onset of this refractoriness was associated with the beginning of an immunosuppressive state known as "immunological eclipse" characterized by a loss of the antitumor immune response when tumor grows beyond a critical size. This immunological eclipse was accompanied by the emergence of a systemic inflammatory condition. Treatment of tumor-bearing mice with a single dose of a synthetic corticosteroid, dexamethasone (DX), reduced significantly all parameters of systemic inflammation and simultaneously reversed the immunological eclipse. The reversion of the eclipse upon DX treatment was not curative itself, but allowed an immunological therapy based in dendritic cells pulsed with tumor antigens, which was itself absolutely ineffective, to exert a significant inhibitory effect against an established growing tumor. The two-step schedule using an anti-inflammatory treatment to reverse the immunological eclipse plus a dendritic cell-based vaccination strategy aimed to stimulate the antitumor immune response, could serve eventually as a model of immunotherapy against animal and human tumors.
- Published
- 2007
39. Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different.
- Author
-
Rimoldi M, Chieppa M, Larghi P, Vulcano M, Allavena P, and Rescigno M
- Subjects
- Animals, Cells, Cultured, Chemokine CCL20, Chemokines, CC metabolism, Dendritic Cells metabolism, Epithelial Cells cytology, Epithelial Cells metabolism, Flagella physiology, Gram-Positive Bacteria cytology, Gram-Positive Bacteria pathogenicity, Humans, Interleukin-10 metabolism, Interleukin-12 metabolism, Macrophage Inflammatory Proteins metabolism, Mice, Monocytes immunology, Monocytes metabolism, Th1 Cells immunology, Th2 Cells immunology, Cell Differentiation, Dendritic Cells cytology, Dendritic Cells immunology, Epithelial Cells immunology, Epithelial Cells microbiology, Gram-Positive Bacteria physiology, Monocytes cytology
- Abstract
Dendritic cells (DCs) are able to open the tight junctions between adjacent epithelial cells (ECs) and to take up both invasive and noninvasive bacteria directly from the intestinal lumen. In this study, we describe a tight cross talk between ECs and human monocyte-derived DCs (MoDCs) in bacterial handling across epithelial monolayers. We show that the release of proinflammatory mediators by ECs in response to bacteria is dependent on bacterial invasiveness and on the presence of flagella. This correlates with the capacity of EC-derived factors to modulate MoDC function. MoDCs incubated with supernatants of bacteria-treated ECs are "noninflammatory" as they release interleukin-10 (IL-10) but not IL-12 and can drive only T helper (Th)-2 type T cells. Moreover, noninflammatory MoDCs release chemokines aimed at recruiting Th2 and T-regulatory cells. In contrast, when MoDCs are incubated with ECs and bacteria in a transwell coculture system, and can contact directly the bacteria across stimulated EC monolayers, they are more inflammatory as they release IL-12 and IL-10 and induce both Th1 and Th2 responses. These results suggest that ECs are not simply a barrier to bacteria entering via the oral route, but they actively influence the activating properties of DCs.
- Published
- 2005
- Full Text
- View/download PDF
40. Intestinal epithelial cells control dendritic cell function.
- Author
-
Rimoldi M, Chieppa M, Vulcano M, Allavena P, and Rescigno M
- Subjects
- Animals, Bacillus subtilis immunology, Chemokines immunology, Coculture Techniques, Cytokines immunology, Dendritic Cells cytology, Humans, Intestinal Mucosa cytology, Lactobacillus plantarum immunology, Mice, Salmonella typhimurium genetics, Salmonella typhimurium immunology, Tight Junctions immunology, Bacterial Infections immunology, Dendritic Cells immunology, Intestinal Mucosa immunology
- Abstract
Dendritic cells (DCs) comprise a family of cells specializing in antigen capture and presentation to T cells. We have recently shown that DC play an active role in bacterial uptake across mucosal surfaces. Indeed, DC are able to open tight junctions and to sample antigens directly across epithelia, both in vitro and in vivo. Because DC express tight junction proteins, the integrity of the epithelial barrier is preserved. In this study we have analyzed the possible involvement of epithelial cells in controlling DC function. We developed an in vitro model in our laboratory consisting of a three-player system of dendritic cells, epithelial cell monolayers, and bacteria. The crosstalk between epithelial cells and dendritic cells was analyzed, and epithelial cells were tested for their capacity to release cytokines and chemokines that induce the migration and activation of DC. We show that the capacity of epithelial cells to produce cytokines and activate DC is dependent on the invasiveness of the bacteria tested. In particular, invasive bacteria stimulate epithelial cells to release proinflammatory cytokines and to induce the maturation state of DC. By contrast, noninvasive bacteria are unable to stimulate epithelial cells, but can activate DC directly when DC translocate to the apical side. In conclusion, epithelial cells are not simply a barrier to bacteria entering via the oral route, but actively influence the activating properties of bystander DC.
- Published
- 2004
- Full Text
- View/download PDF
41. Toll receptor-mediated regulation of NADPH oxidase in human dendritic cells.
- Author
-
Vulcano M, Dusi S, Lissandrini D, Badolato R, Mazzi P, Riboldi E, Borroni E, Calleri A, Donini M, Plebani A, Notarangelo L, Musso T, and Sozzani S
- Subjects
- Adolescent, Adult, Cell Differentiation immunology, Cell Line, Tumor, Cells, Cultured, Child, Child, Preschool, Dendritic Cells metabolism, Dendritic Cells pathology, Escherichia coli growth & development, Escherichia coli immunology, Female, Granulomatous Disease, Chronic immunology, Granulomatous Disease, Chronic microbiology, Granulomatous Disease, Chronic pathology, Humans, Intracellular Fluid immunology, Intracellular Fluid microbiology, Ligands, Lipopolysaccharides pharmacology, Membrane Glycoproteins metabolism, NADPH Oxidases physiology, Phagocytosis immunology, Receptors, Cell Surface metabolism, Respiratory Burst immunology, Toll-Like Receptors, Up-Regulation immunology, Dendritic Cells enzymology, Dendritic Cells immunology, Membrane Glycoproteins physiology, NADPH Oxidases metabolism, Receptors, Cell Surface physiology
- Abstract
Activation of NADPH oxidase represents an essential mechanism of defense against pathogens. Dendritic cells (DC) are phagocytic cells specialized in Ag presentation rather than in bacteria killing. Human monocyte-derived DC were found to express the NADPH oxidase components and to release superoxide anions in response to phorbol esters and phagocytic agonists. The NADPH oxidase components p47phox and gp91phox were down-regulated during monocyte differentiation to DC, and maturation of DC with pathogen-derived molecules, known to activate TLRs, increased p47phox and gp91phox expression and enhanced superoxide anions release. Similar results were obtained with plasmacytoid DC following maturation with influenza virus. In contrast, activation of DC by immune stimuli (CD40 ligand) did not regulate NADPH oxidase components or respiratory burst. NADPH oxidase-derived oxygen radicals did not play any role in DC differentiation, maturation, cytokine production, and induction of T cell proliferation, as based on the normal function of DC generated from chronic granulomatous disease patients and the use of an oxygen radical scavenger. However, NADPH oxidase activation was required for DC killing of intracellular Escherichia coli. It is likely that the selective regulation of oxygen radicals production by pathogen-activated DC may function to limit pathogen dissemination during DC trafficking to secondary lymphoid tissues.
- Published
- 2004
- Full Text
- View/download PDF
42. CD40 activation of BCP-ALL cells generates IL-10-producing, IL-12-defective APCs that induce allogeneic T-cell anergy.
- Author
-
D'Amico G, Vulcano M, Bugarin C, Bianchi G, Pirovano G, Bonamino M, Marin V, Allavena P, Biagi E, and Biondi A
- Subjects
- Antigens, CD immunology, Bone Marrow Cells immunology, Child, Humans, Interleukin-12 genetics, Interleukin-12 immunology, Lymphocyte Activation, Receptors, CCR7, Receptors, Chemokine immunology, Antigen-Presenting Cells immunology, B-Lymphocytes immunology, CD40 Antigens immunology, Clonal Anergy immunology, Interleukin-10 immunology, Interleukin-12 deficiency, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, T-Lymphocytes immunology
- Abstract
The use of leukemia cells as antigen-presenting cells (APCs) in immunotherapy is critically dependent on their capacity to initiate and sustain an antitumor-specific immune response. Previous studies suggested that pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells could be manipulated in vitro through the CD40-CD40L pathway to increase their immunostimulatory capacity. We extended the APC characterization of CD40L-activated BCP-ALL for their potential use in immunotherapy in a series of 19 patients. Engaging CD40 induced the up-regulation of CCR7 in 7 of 11 patients and then the migration to CCL19 in 2 of 5 patients. As accessory cells, CD40L-activated BCP-ALL induced a strong proliferation response of naive T lymphocytes. Leukemia cells, however, were unable to sustain proliferation over time, and T cells eventually became anergic. After CD40-activation, BCP-ALL cells released substantial amounts of interleukin-10 (IL-10) but were unable to produce bioactive IL-12 or to polarize TH1 effectors. Interestingly, adding exogenous IL-12 induced the generation of interferon-gamma (IFN-gamma)-secreting TH1 effectors and reverted the anergic profile in a secondary response. Therefore, engaging CD40 on BCP-ALL cells is insufficient for the acquisition of full functional properties of immunostimulatory APCs. These results suggest caution against the potential use of CD40L-activated BCP-ALL cells as agents for immunotherapy unless additional stimuli, such as IL-12, are provided.
- Published
- 2004
- Full Text
- View/download PDF
43. Differential recognition and scavenging of native and truncated macrophage-derived chemokine (macrophage-derived chemokine/CC chemokine ligand 22) by the D6 decoy receptor.
- Author
-
Bonecchi R, Locati M, Galliera E, Vulcano M, Sironi M, Fra AM, Gobbi M, Vecchi A, Sozzani S, Haribabu B, Van Damme J, and Mantovani A
- Subjects
- Animals, Binding, Competitive immunology, CHO Cells, Cell Line, Cell Line, Tumor, Chemokine CCL17, Chemokine CCL22, Chemokines, CC physiology, Clone Cells, Cricetinae, Dendritic Cells immunology, Dendritic Cells metabolism, Dipeptidyl Peptidase 4 physiology, Endothelium, Lymphatic immunology, Endothelium, Lymphatic metabolism, Humans, Inflammation immunology, Inflammation metabolism, Mice, Protein Isoforms metabolism, Protein Processing, Post-Translational, Receptors, CCR10, Receptors, CCR4, Receptors, Chemokine agonists, Receptors, Chemokine biosynthesis, Receptors, Chemokine physiology, Sequence Deletion, Transfection, Chemokine Receptor D6, Chemokines, CC metabolism, Macrophages immunology, Macrophages metabolism, Receptors, Chemokine metabolism
- Abstract
The promiscuous D6 receptor binds several inflammatory CC chemokines and has been recently proposed to act as a chemokine-scavenging decoy receptor. The present study was designed to better characterize the spectrum of CC chemokines scavenged by D6, focusing in particular on CCR4 ligands and analyzing the influence of NH(2)-terminal processing on recognition by this promiscuous receptor. Using D6 transfectants, it was found that D6 efficiently bound and scavenged most inflammatory CC chemokines (CCR1 through CCR5 agonists). Homeostatic CC chemokines (CCR6 and CCR7 agonists) were not recognized by D6. The CCR4 agonists CC chemokine ligand 17 (CCL17) and CCL22 bound to D6 with high affinity. CCL17 and CCL22 have no agonistic activity for D6 (chemotaxis and calcium fluxes), but were rapidly scavenged, resulting in reduced chemotactic activity on CCR4 transfectants. CD26 mediates NH(2) terminus processing of CCL22, leading to the production of CCL22 (3-69) and CCL22 (5-69) that do not interact with CCR4. These NH(2)-terminal truncated forms of CCL22 were not recognized by D6. The results presented in this study show that D6 recognizes and scavenges a wide spectrum of inflammatory CC chemokines, including the CCR4 agonists CCL22 and CCL17. However, this promiscuous receptor is not engaged by CD26-processed, inactive, CCL22 variants. By recognizing intact CCL22, but not its truncated variants, D6 expressed on lymphatic endothelial cells may regulate the traffic of CCR4-expressing cells, such as dendritic cells.
- Published
- 2004
- Full Text
- View/download PDF
44. Hypothesis: an alternative pathway for the regulation of inflammation.
- Author
-
Isturiz MA, Beigier-Bompadre M, Barrionuevo P, Alves-Rosa F, Palermo MS, and Vulcano M
- Subjects
- Gene Expression Regulation immunology, Gene Expression Regulation physiology, Humans, Inflammation physiopathology, Interferon-gamma metabolism, Monocytes immunology, Monocytes metabolism, Neutrophils metabolism, Receptors, IgG metabolism, Tumor Necrosis Factor-alpha physiology, Antigen-Antibody Complex immunology, Inflammation immunology, N-Formylmethionine Leucyl-Phenylalanine pharmacology, Neutrophils immunology, Receptors, IgG immunology, Tumor Necrosis Factor-alpha drug effects
- Abstract
Regulation of inflammation is a crucial event since its alteration, such as in sepsis and chronic autoimmune (i.e. rheumatoid arthritis, lupus erythematosus) or infectious diseases (i.e. tuberculosis, leprosy), determines severe tissue damage. Although there is a general consensus that regulation of inflammation results from a balance between proinflammatory and antiinflammatory pathways, we arrived at the conclusion that well known chemoattractants/proinflammatory molecules such as bacterial formyl peptides or immune complexes (IC), could induce, paradoxically, strong antiinflammatory effects. Thus, we demonstrated that N-formyl-methionyl-leucyl-phenylalanine (FMLP) exerted a drastic antiinflammatory effect, inhibiting the secretion of tumor necrosis alpha (TNF-alpha) induced by lipopolysaccharides, a potent TNF-alpha inducer. We also determined that in human neutrophils FMLP and IC induced the downregulation of receptors for the Fc portion of IgG (FcgammaRII and FcgammaRIIIB). Moreover, FMLP inhibited interferon gamma (IFN-gamma)-induced FcgammaRI expression and IC downregulate class II molecules of the major histocompatibility complex on monocytes. Part of these effects were mediated by the release of aspartic-, serin-, or metalloproteases. All these results favor the postulation of a new concept on the regulation of inflammation carried out through an alternative and non conventional pathway, in which a chemoattractant/proinflammatory agent could, under certain circumstances, act as an antiinflammatory molecule.
- Published
- 2004
45. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids.
- Author
-
Wittamer V, Franssen JD, Vulcano M, Mirjolet JF, Le Poul E, Migeotte I, Brézillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, and Communi D
- Subjects
- Amino Acid Sequence, Calcium metabolism, Cell Movement, Chemokines chemistry, Chemokines genetics, Chemokines isolation & purification, Dendritic Cells physiology, Humans, Intercellular Signaling Peptides and Proteins, Molecular Sequence Data, Antigen-Presenting Cells physiology, Chemokines physiology, Receptors, Chemokine metabolism
- Abstract
Dendritic cells (DCs) and macrophages are professional antigen-presenting cells (APCs) that play key roles in both innate and adaptive immunity. ChemR23 is an orphan G protein-coupled receptor related to chemokine receptors, which is expressed specifically in these cell types. Here we present the characterization of chemerin, a novel chemoattractant protein, which acts through ChemR23 and is abundant in a diverse set of human inflammatory fluids. Chemerin is secreted as a precursor of low biological activity, which upon proteolytic cleavage of its COOH-terminal domain, is converted into a potent and highly specific agonist of ChemR23, the chemerin receptor. Activation of chemerin receptor results in intracellular calcium release, inhibition of cAMP accumulation, and phosphorylation of p42-p44 MAP kinases, through the Gi class of heterotrimeric G proteins. Chemerin is structurally and evolutionary related to the cathelicidin precursors (antibacterial peptides), cystatins (cysteine protease inhibitors), and kininogens. Chemerin was shown to promote calcium mobilization and chemotaxis of immature DCs and macrophages in a ChemR23-dependent manner. Therefore, chemerin appears as a potent chemoattractant protein of a novel class, which requires proteolytic activation and is specific for APCs.
- Published
- 2003
- Full Text
- View/download PDF
46. Unique regulation of CCL18 production by maturing dendritic cells.
- Author
-
Vulcano M, Struyf S, Scapini P, Cassatella M, Bernasconi S, Bonecchi R, Calleri A, Penna G, Adorini L, Luini W, Mantovani A, Van Damme J, and Sozzani S
- Subjects
- Cell Differentiation drug effects, Cell Differentiation immunology, Cells, Cultured, Chemokines, CC antagonists & inhibitors, Chemokines, CC metabolism, Chemokines, CC physiology, Chemotaxis, Leukocyte immunology, Cholecalciferol pharmacology, Dendritic Cells cytology, Dexamethasone pharmacology, Dinoprostone pharmacology, Growth Inhibitors pharmacology, Humans, Immunosuppressive Agents pharmacology, Interferon-gamma pharmacology, Interleukin-10 pharmacology, Myeloid Cells cytology, Myeloid Cells immunology, Myeloid Cells metabolism, Plasma Cells cytology, Plasma Cells immunology, Plasma Cells metabolism, Chemokines, CC biosynthesis, Dendritic Cells immunology, Dendritic Cells metabolism
- Abstract
Dendritic cells (DC) orchestrate the trafficking of lymphocytes by secreting chemokines with different specificity and function. Chemokines are produced at higher levels by mature DC. This study shows that CCL18 is one of the most abundant chemokines produced by immature DC. In contrast to all other chemokines investigated to date, CCL18 was selectively down-regulated during the maturation process induced by LPS, TNF, CD40 ligand, Staphylococcus aureus Cowan I, Candida albicans, and influenza virus. IL-10 and vitamin D(3), two known inhibitors of DC differentiation and function, strongly promoted CCL18 secretion, whereas IFN-gamma, a costimulator of DC function, inhibited its production. IL-10 also induced CCL18 secretion in blood myeloid DC. No CCL18 secretion was observed in blood plasmacytoid DC. The opposite pattern of regulation was observed for CCL20, a prototypic inflammatory chemokine. CCL18 was found to be a chemotactic factor for immature DC. Therefore, CCL18 may act as a chemotactic signal that promotes the colocalization of immature DC with naive T lymphocytes in an IL-10-dominated environment with the consequent generation of T regulatory cells. These characteristics suggest that CCL18 may be part of an inhibitory pathway devoted to limiting the generation of specific immune responses at peripheral sites.
- Published
- 2003
- Full Text
- View/download PDF
47. Cutting edge: differential chemokine production by myeloid and plasmacytoid dendritic cells.
- Author
-
Penna G, Vulcano M, Roncari A, Facchetti F, Sozzani S, and Adorini L
- Subjects
- Cell Lineage immunology, Cells, Cultured, Chemokine CCL17, Chemokine CCL22, Chemokine CCL3, Chemokine CCL4, Chemokines blood, Chemokines, CC biosynthesis, Dendritic Cells classification, Humans, Macrophage Inflammatory Proteins biosynthesis, Chemokines biosynthesis, Dendritic Cells immunology, Dendritic Cells metabolism, Myeloid Cells immunology, Myeloid Cells metabolism
- Abstract
To examine the different roles of myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) in the induction and regulation of immune response, we have studied chemokine secretion by freshly isolated DC subsets in response to bacterial, viral, and T cell-derived stimuli. M-DCs selectively produced very high levels of the homeostatic chemokines CC chemokine ligand (CCL)17 and CCL22, while P-DCs produced very little if any. In contrast, the proinflammatory chemokine CCL3 was secreted mostly by P-DCs, whereas CCL4 and CXC chemokine ligand 8 were produced by both subsets. The selective production of CCL17 and CCL22 by M-DCs but not P-DCs was confirmed in vivo by immunohistology on human reactive lymph node sections. The high production of CCR4 ligands by M-DCs suggests their capacity to selectively recruit at sites of inflammation T cells with regulatory properties or with a Th2 phenotype, whereas P-DCs, by preferentially secreting CCR1/CCR5 ligands, would mostly recruit effector T cells and, in particular, Th1-type cells.
- Published
- 2002
- Full Text
- View/download PDF
48. Differential migration behavior and chemokine production by myeloid and plasmacytoid dendritic cells.
- Author
-
Penna G, Vulcano M, Sozzani S, and Adorini L
- Subjects
- Cell Movement immunology, Chemokines blood, Dendritic Cells cytology, Dendritic Cells immunology, Humans, Myeloid Cells immunology, Plasma Cells cytology, Plasma Cells immunology, Chemokines biosynthesis, Dendritic Cells metabolism, Myeloid Cells metabolism, Plasma Cells metabolism
- Abstract
The existence of dendritic cell (DC) subsets is firmly established, but their trafficking properties are still largely unknown. We have indicated that myeloid dendritic cells (M-DCs) and plasmacytoid dendritic cells (P-DCs) isolated from human blood differ widely in the capacity to migrate to chemotactic stimuli. The pattern of chemokine receptors expressed ex vivo by both subsets is similar, but P-DCs display, compared with M-DCs, higher levels of CC chemokine receptor (CCR)5, CCR7, and CXCR3. Intriguingly, most chemokine receptors of P-DCs, in particular those specific for inflammatory chemokines and classical chemotactic agonists, are not functional in circulating cells. Following maturation induced by cluster designation (CD)40 ligation, the receptors for inflammatory chemokines are downregulated and CCR7 on P-DCs becomes coupled to migration. The drastically impaired capacity of blood P-DCs to migrate in response to inflammatory chemotactic signals contrasts with the response to lymph node-homing chemokines, indicating a propensity to migrate to secondary lymphoid organs rather than to sites of inflammation. The distinct migration behavior of DC subsets is accompanied by a different profile of chemokine production. In contrast to the high production by M-DCs, the homeostatic CC chemokine ligand (CCL)17/ thymus- and activation-regulated chemokine (TARC) is not produced by PDCs in response to any stimulus tested and their production of CCL22/MDC is minimal, if any, compared with M-DCs. Thus, stimulated M-DCs, but not P-DCs, are able to produce high levels of chemokines recruiting T-helper 2 cells (Th2) and T-regulatory cells. Conversely, the proinflammatory chemokine CCL3/macrophage inflammatory protein (MIP)-1alpha is predominantly produced by P-DCs. Therefore, P-DCs appear to produce preferentially proinflammatory chemokines, but to respond selectively to homeostatic ones, whereas the reverse is true for M-DCs, highlighting not only the different migratory properties of these DC subsets, but also their capacity to recruit different cell types at inflammation sites.
- Published
- 2002
- Full Text
- View/download PDF
49. Commitment of juvenile myelo-monocytic (JMML) leukemic cells to spontaneously differentiate into dendritic cells.
- Author
-
Longoni D, D'Amico G, Gaipa G, Bernasconi S, Vulcano M, Onnis P, Niemeyer CM, Allavena P, and Biondi A
- Subjects
- Antigen Presentation immunology, Case-Control Studies, Child, Child, Preschool, Dendritic Cells immunology, Endocytosis, Humans, Immunity, Cellular, Infant, Interleukin-10 biosynthesis, Interleukin-10 immunology, Interleukin-12 biosynthesis, Interleukin-12 immunology, Lymphocyte Activation immunology, Lymphocyte Culture Test, Mixed, Monocytes pathology, Cell Differentiation physiology, Dendritic Cells cytology, Leukemia, Myelomonocytic, Acute pathology
- Abstract
Juvenile myelo-monocytic leukemia (JMML) is a severe malignant stem cell disorder of childhood. A proportion of cells from JMML mononuclear cells (MNC) spontaneously differentiate in vitro into dendritic cells (DC). We have studied MNC from 14 JMML patients, and characterized their functional activity as antigen presenting cells (APC). Large cells, differentiated after seven days of culture, expressed high levels of MHC II molecules and Mannose Receptor, variable levels of CD80 and CD86, and low levels of CD1a. Similar to immature DC, cells from JMML had high levels of dextran endocytosis, and were able to elicit proliferation of allogeneic T lymphocytes in mixed leukocyte reaction (MLR). CD40L-matured DC from JMML was associated with relevant increase of CD80, CD86 and CD83, increased APC activity, responded in chemotaxis assays to MIP-3beta and secreted increased amounts of macrophage derived chemokine (MDC). Immature DC and CD40L-matured DC from JMML produced very low amounts of IL-12, whereas the production of IL-10 was higher than normal DC. In line with these findings, they showed defective capacity to polarize naive T cells to differentiate into Th1 effectors. These results indicate that MNC from JMML are committed to spontaneously differentiate into DC with morphological and phenotypical characteristics similar to normal DC. The cytokine profile produced by these APC is likely to suppress and not to elicit a protective immune response.
- Published
- 2002
- Full Text
- View/download PDF
50. Dendritic cells as a major source of macrophage-derived chemokine/CCL22 in vitro and in vivo.
- Author
-
Vulcano M, Albanesi C, Stoppacciaro A, Bagnati R, D'Amico G, Struyf S, Transidico P, Bonecchi R, Del Prete A, Allavena P, Ruco LP, Chiabrando C, Girolomoni G, Mantovani A, and Sozzani S
- Subjects
- Cells, Cultured, Chemokine CCL22, Chemokines, CC biosynthesis, Cholecalciferol pharmacology, Chromatography, High Pressure Liquid, Dendritic Cells drug effects, Dendritic Cells metabolism, Dermatitis immunology, Dermatitis metabolism, Dexamethasone pharmacology, Dinoprostone pharmacology, Endocytosis, Histiocytosis, Langerhans-Cell immunology, Histiocytosis, Langerhans-Cell metabolism, Humans, Leukocytes immunology, Leukocytes metabolism, Lipopolysaccharides pharmacology, Lymphatic Diseases immunology, Lymphatic Diseases metabolism, Mass Spectrometry, Monocytes immunology, Protein Isoforms biosynthesis, RNA, Messenger biosynthesis, Transcriptional Activation drug effects, Chemokines, CC genetics, Dendritic Cells immunology
- Abstract
Macrophage-derived chemokine (MDC)/CCL22 is a CC chemokine active on dendritic cells (DC), NK cells and Th2 lymphocytes. The present study was aimed at comprehensively investigating MDC production in vitro and in vivo. DC were the most potent producers of MDC among leukocytes tested. Endothelial cells did not produce MDC under a variety of conditions. Signals that induce maturation (lipopolysaccharide, IL-1, TNF, CD40 ligand, recognition of bacteria and yeast) dramatically augmented MDC production, and dexamethasone and vitamin D3 blocked it. Prostaglandin E(2), which blocked the acquisition of IL-12 production and the capacity to promote Th1 generation, did not affect MDC production. Using mass spectrometry-based techniques, DC supernatants were found to contain N-terminally truncated forms of MDC [MDC(3-69), MDC(5-69) and MD(C7-69)] as well as the full-length molecule. In vivo, CD1a(+), CD83(+), MDC(+) DC were found in reactive lymph nodes, and in Langerhans' cell histiocytosis. Skin lesions of atopic dermatitis patients showed that CD1a(+) or CD1b(+) DC, and DC with a CD83(+) phenotype were responsible for MDC production in this Th2-oriented disorder. Thus, DC are the predominant source of MDC in vitro and in vivo under a variety of experimental and clinical conditions. Processing of MDC to MDC(3-69) and shorter forms which do not recognize CCR4 is likely to represent a feedback mechanism of negative regulation.
- Published
- 2001
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.