title: Ex vivo all-trans retinoic acid modulates NO production and regulates IL-6 effect during rheumatoid arthritis: a study in Algerian patients.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease. The pathophysiology of RA implicates several mediators such as nitric oxide (NO) and cytokines such as interleukin-6 (IL-6), which is deeply involved in the main characteristics of RA. Furthermore, all-trans retinoic acid (ATRA) is an active vitamin A derivative well-known to have diverse immunomodulatory actions. In our study, we investigated first, the ex vivo immunomodulatory potential of ATRA on NO pathway by peripheral blood mononuclear cells (PBMCs) from Algerian RA patients. Then, we assessed the possible regulatory effect of ATRA on NO production induced by IL-6. PBMCs isolated from active and inactive RA patients and healthy controls were cultured with different concentrations of IL-6 or/with ATRA. NO production was assessed using the Griess method. Inducible nitric oxide synthase expression and NF-κB activity were analyzed by immunofluorescence test. Our results revealed a high NO production during active RA. We noticed that while IL-6 induced a high NO production and iNOS expression, ATRA downregulated both. ATRA also inhibited nuclear NF-κB translocation. Interestingly, it seems that NO production mediated by IL-6 on PBMCs of RA patients is downregulated by ATRA. Taken together, our results highlight the immunomodulatory effect of ATRA on NO pathway in RA patients and its possible role in regulating IL-6-mediated NO production. All these findings suggest its potential therapeutic role during RA.
authors.affiliation: a Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences , USTHB (University of Sciences and Technology) , Algiers , Algeria.
authors.forename: Amina
authors.initials: A
authors.lastname: Arroul-Lammali
authors.affiliation: b Rheumatology Department , Ben aknoun hospital EHS , Algiers , Algeria.
authors.forename: Fadia
authors.initials: F
authors.lastname: Rahal
authors.affiliation: b Rheumatology Department , Ben aknoun hospital EHS , Algiers , Algeria.
authors.forename: Radia
authors.initials: R
authors.lastname: Chetouane
authors.affiliation: a Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences , USTHB (University of Sciences and Technology) , Algiers , Algeria.
authors.forename: Zineb
authors.initials: Z
authors.lastname: Djeraba
authors.affiliation: a Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences , USTHB (University of Sciences and Technology) , Algiers , Algeria.
authors.forename: Oussama
authors.initials: O
authors.lastname: Medjeber
authors.affiliation: b Rheumatology Department , Ben aknoun hospital EHS , Algiers , Algeria.
authors.forename: Aicha
authors.initials: A
authors.lastname: Ladjouze-Rezig
authors.affiliation: a Laboratory of Cellular and Molecular Biology (LBCM), Cytokines and NO Synthases Team, Faculty of Biological Sciences , USTHB (University of Sciences and Technology) , Algiers , Algeria.
authors.forename: Chafia
authors.initials: C
authors.lastname: Touil-Boukoffa
mesh_terms: D000328:Adult; D000368:Aged; D000462:Algeria; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000276:immunology*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D009569:Nitric Oxide; D014212:Tretinoin
keywords: Rheumatoid arthritis; all-trans retinoic acid; inducible nitric oxide synthase; interleukin 6; nitric oxide