title: Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of B cell and antibody production.
abstract: Oxidative stress is involved in the pathophysiology of rheumatoid arthritis (RA). We investigated the therapeutic potential of rebamipide, a gastroprotective agent with a property of reactive oxygen species scavenger, on the development of inflammatory polyarthritis and the pathophysiological mechanisms by which rebamipide might confer anti-arthritic effects in SKG mice, an animal model of RA. Intraperitoneal (i.p.) injection of rebamipide attenuated the severity of clinical and histological arthritis. Rebampide treatment reduced the number of T helper type 1 (Th1), Th2, Th17, inducible T cell co-stimulator (ICOS)(+) follicular helper T (Tfh) transitional type (T2) and mature B cells in the spleen, but increased the number of regulatory T (Treg ), CD19(+) CD1d(high) CD5(high) , CD19(+) CD25(high) forkhead box protein 3 (FoxP3)(+) regulatory B (Breg ) cells, memory B cells, and transitional type 1 (T1) B cells. In addition, flow cytometric analysis revealed significantly decreased populations of FAS(+) GL-7(+) germinal centre B cells and B220(-) CD138(+) plasma cells in the spleens of rebamipide-treated SKG mice compared to controls. Rebamipide decreased germinal centre B cells and reciprocally induced Breg cells in a dose-dependent manner in vitro. Rebamipide-induced Breg cells had more suppressive capacity in relation to T cell proliferation and also inhibited Th17 differentiation from murine CD4(+) T cells. Together, these data show that i.p. administration of rebamipide suppresses arthritis severity by inducing Breg and Treg cells and suppressing Tfh and Th17 cells in a murine model of RA.
authors.affiliation: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Korea; Laboratory of Immune Network, Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: J-K
authors.initials: JK
authors.lastname: Byun
authors.forename: S-J
authors.initials: SJ
authors.lastname: Moon
authors.forename: J-Y
authors.initials: JY
authors.lastname: Jhun
authors.forename: E-K
authors.initials: EK
authors.lastname: Kim
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Youn
authors.forename: J-K
authors.initials: JK
authors.lastname: Min
authors.forename: S-H
authors.initials: SH
authors.lastname: Park
authors.forename: H-Y
authors.initials: HY
authors.lastname: Kim
authors.forename: M-L
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015363:Quinolones / Q000276:immunology / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D015363:Quinolones; C052785:rebamipide; D000409:Alanine
keywords: B cells; T cells; arthritis (including rheumatoid arthritis)
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