title: Rebamipide prevents peripheral arthritis and intestinal inflammation by reciprocally regulating Th17/Treg cell imbalance in mice with curdlan-induced spondyloarthritis.
abstract: Spondyloarthritis (SpA) usually manifests as arthritis of the axial and peripheral joints but can also result in extra-articular manifestations such as inflammatory bowel disease. Proinflammatory cytokine interleukin-17 (IL-17) plays a crucial role in the pathogenesis of SpA. Rebamipide inhibits signal transducer and activator of transcription 3 that controls IL-17 production and Th17 cell differentiation. This study examined the effect of rebamipide on SpA development.
  
  
  
  SKG ZAP-70(W163C) mice were immunized with curdlan to induce SpA features. The mice were then intraperitoneally injected with rebamipide or vehicle 3 times a week for 14 weeks and their clinical scores were evaluated. Histological scores of the paw and spine and the length of the gut were measured at sacrifice. Immunohistochemical staining of IL-17 and tumor necrosis factor-α (TNF-α) was performed using tissue samples isolated from the axial joints, peripheral joints, and gut. Spleen tissue samples were isolated from both rebamipide- or vehicle-treated mice with SpA at 14 weeks after curdlan injection to determine the effect of rebamipide on Th17 and regulatory T (Treg) cell differentiation.
  
  
  
  Rebamipide decreased the clinical and histological scores of the peripheral joints. The total length of the gut was preserved in rebamipide-treated mice. IL-17 and TNF-α expression in the spine, peripheral joints, and gut was lower in rebamipide-treated mice than in control mice. Th17 cell differentiation was suppressed whereas Treg cell differentiation was upregulated in the spleen of rebamipide-treated mice.
  
  
  
  Rebamipide exerted beneficial effects in mice with SpA by preventing peripheral arthritis and intestinal inflammation and by regulating Th17/Treg cell imbalance, suggesting that it can be used as a potential therapeutic agent for treating arthritis to SpA patients.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea.|Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Hong-Ki
authors.initials: HK
authors.lastname: Min
authors.affiliation: Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Seon-Yeong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea.|Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea.|Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kwok
authors.affiliation: Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea. iammila@catholic.ac.kr.
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, 137-701, South Korea. rapark@catholic.ac.kr.|Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, 137-040, South Korea. rapark@catholic.ac.kr.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Park
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D007422:Intestines / Q000473:pathology*; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008807:Mice, Inbred BALB C; D015363:Quinolones / Q000494:pharmacology / Q000627:therapeutic use*; D013131:Spine / Q000187:drug effects / Q000473:pathology; D025241:Spondylarthritis / Q000188:drug therapy / Q000276:immunology* / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D047071:beta-Glucans
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D015363:Quinolones; D014409:Tumor Necrosis Factor-alpha; D047071:beta-Glucans; C038459:curdlan; C052785:rebamipide; D000409:Alanine
keywords: Rebamipide; Regulatory T cell; Spondyloarthritis; Type 17 helper T cell