Rebamipide attenuates autoimmune arthritis severity in SKG mice via regulation of B cell and antibody production
- 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.
- Issue Date
- Oct-2014
- Publisher
- WILEY-BLACKWELL
- Keywords
- arthritis (including rheumatoid arthritis); B cells; T cells
- Citation
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY, v.178, no.1, pp.9 - 19
- Indexed
- SCIE
SCOPUS
- Journal Title
- CLINICAL AND EXPERIMENTAL IMMUNOLOGY
- Volume
- 178
- Number
- 1
- Start Page
- 9
- End Page
- 19
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/158993
- DOI
- 10.1111/cei.12355
- ISSN
- 0009-9104
- 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 (T-reg), CD19⁺ CD1d(high) CD5(high), CD19⁺ CD25(high) forkhead box protein 3 (FoxP3)⁺ regulatory B (B-reg) 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 B-reg cells in a dose-dependent manner in vitro. Rebamipide-induced B-reg 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 B-reg and T-reg cells and suppressing Tfh and Th17 cells in a murine model of RA.
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