Sarah Benchabane1,2, Mourad Belkhelfa1, Houda Belguendouz1, Sourour Zidi1,3,4, Abdelhalim Boudjelida5, Pierre Youinou6, Chafia Touil-Boukoffa7. 1. Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Group, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria. 2. Department of Biology and Cellular Physiology, Faculty of Biological Sciences, Saad Dahlab's University of Blida, Blida, Algeria. 3. Department of Biology, University of Guelma, Guelma, Algeria. 4. Badji Mokhtar University, Annaba, Algeria. 5. Internal Medicine Department, Maillot Hospital, Algiers, Algeria. 6. Laboratory of Excellence (Labex) IGO, and INSERM ERI29, European University of Brittany, Brest, France. 7. Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Group, Faculty of Biological Sciences, University of Sciences and Technology Houari Boumediene (USTHB), Algiers, Algeria. touilboukoffa@yahoo.fr.
Abstract
BACKGROUND: Primary Sjögren's syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-β on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-β treatment on NO production, and pSS clinical and serological manifestations. METHODS: In 41 pSS patients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSS patients. RESULTS: Our results revealed a strong down-modulating effect of IFN-β in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-β exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-β on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-β on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression. CONCLUSION: Our findings highlight a consistent ex vivo inhibitory effect of IFN-β on pro-inflammatory cytokine production and NO pathway in pSS patients. Our data suggest that IFN-β could represent a potential candidate for targeting inflammation during pSS.
BACKGROUND: Primary Sjögren's syndrome (pSS) represents a chronic, systemic autoimmune disorder, characterized by lymphocytic infiltration of exocrine glands, inducing compromised secretory function and tissue destruction. Increasing evidence had revealed that inflammatory mediators, such as nitric oxide (NO) and pro-inflammatory cytokines, are critical in the development and perpetuation of pSS systemic manifestations. In our current study, we aimed to investigate the ex vivo immunomodulatory effect of interferon (IFN)-β on iNOS expression, as well as on pro-inflammatory (tumor necrosis factor (TNF)-α, interleukin (IL)-6) and immunoregulatory (IL-10) cytokine production. Furthermore, we examined potential associations between the influence of IFN-β treatment on NO production, and pSS clinical and serological manifestations. METHODS: In 41 pSSpatients documented for their clinical and serological features, NO and cytokines levels were measured by the Griess method and enzyme-linked immunosorbent assay, respectively. Inducible nitric oxide synthase expression was analyzed by fluorescence immunostaining assay, using peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and pSSpatients. RESULTS: Our results revealed a strong down-modulating effect of IFN-β in the secretion of pro-inflammatory mediators including TNF-α, IL-6, and NO production. Interestingly, IFN-β exerts an increase in IL-10 levels. The most suppressive effect exerted by IFN-β on NO production was importantly reported for patients with neurological manifestation. This immunomodulatory effect of IFN-β on NO production is highly related to the decrease of inducible nitric oxide synthase (iNOS) expression. CONCLUSION: Our findings highlight a consistent ex vivo inhibitory effect of IFN-β on pro-inflammatory cytokine production and NO pathway in pSSpatients. Our data suggest that IFN-β could represent a potential candidate for targeting inflammation during pSS.
Authors: C Vitali; S Bombardieri; R Jonsson; H M Moutsopoulos; E L Alexander; S E Carsons; T E Daniels; P C Fox; R I Fox; S S Kassan; S R Pillemer; N Talal; M H Weisman Journal: Ann Rheum Dis Date: 2002-06 Impact factor: 19.103