Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of B cell and antibody production. (4th September 2014)

• Record Type: Journal Article
• Authors: Byun, J-K; Moon, S-J; Jhun, J-Y; Kim, E-K; Park, J-S; Youn, J; Min, J-K; Park, S-H; Kim, H-Y; Cho, M-L
• Is Part Of: Clinical and experimental immunology. Volume 178:Number 1(2014:Oct.)
• Page Start: 9
• Page End: 19
• Publication Date: 2014-09-04
• Subjects: arthritis (including rheumatoid arthritis) -- B cells -- T cells; Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12355
• Languages: English
• ISSNs: 0009-9104

Abstract

Summary: 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.