title: Anti-inflammatory effect of all-trans-retinoic acid in inflammatory arthritis.
abstract: OBJECTIVE
  To determine whether all-trans-retinoic acid (ATRA) improves the destruction of joints and the effect of cytokines on DBA/1J mice with collagen-induced arthritis (CIA).
  
  
  METHODS
  Starting from the time of type II collagen injection, DBA/1J mice were injected intraperitoneally with PBS or 0.5 mg of ATRA 3 times per week for 35 days. The effects of treatment were monitored by determining arthritis and histological scores and measuring cellular proliferation, production of cytokines (IL-2, IL-10, IL-12, IL-6, IFN-gamma, and TNF-alpha) and IgG, and the expression of mRNAs for inducible nitric oxide synthase (iNOS), monocyte chemoattractant protein-1 (MCP-1), and CXCR3.
  
  
  RESULTS
  The arthritis score and incidence of arthritis were lower in the mice treated with ATRA than in those treated with PBS. Histopathologic evidence of joint damage was 34% lower, and the infiltrations of macrophages were reduced in the mice treated with ATRA compared with those treated with PBS. Type II collagen- and ConA-stimulated proliferation of spleen cells, the production of cytokines (IL-6, IL-12, and TNF-alpha), the serum levels of total IgG and IgG1 anti-collagen antibodies, and the expression of mRNAs for MCP-1 were significantly reduced in the mice treated with ATRA than in those treated with PBS.
  
  
  CONCLUSIONS
  ATRA improved the clinical course and reduced the production of inflammatory cytokines, immunoglobulin, and chemokines in murine CIA. These data suggest that ATRA might be also effective for the treatment of inflammatory arthritis like human rheumatoid arthritis.
authors.affiliation: Department of Nephrology and Rheumatology, Kinki University School of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yamagata
authors.forename: Masafumi
authors.initials: M
authors.lastname: Sugiyama
authors.forename: Shinya
authors.initials: S
authors.lastname: Ikoma
authors.forename: Koji
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Masanori
authors.initials: M
authors.lastname: Funauchi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003094:Collagen / Q000276:immunology / Q000494:pharmacology; D016207:Cytokines / Q000276:immunology; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000097:blood; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014212:Tretinoin / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; C515187:CXCR3 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C515188:Cxcr3 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D014212:Tretinoin; D003094:Collagen; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse