We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Rebamipide Suppresses Collagen-Induced Arthritis Through Reciprocal Regulation of Th17/Treg Cell Differentiation and Heme Oxygenase 1 Induction.
- Authors
Moon, Su‐Jin; Park, Jin‐Sil; Woo, Yun‐Ju; Lim, Mi‐Ae; Kim, Sung‐Min; Lee, Seon‐Yeong; Kim, Eun‐Kyung; Lee, Hee Jin; Lee, Weon Sun; Park, Sang‐Hi; Jeong, Jeong‐Hee; Park, Sung‐Hwan; Kim, Ho‐Youn; Cho, Mi‐La; Min, Jun‐Ki
- Abstract
Objective Rebamipide, a gastroprotective agent, has the ability to scavenge reactive oxygen radicals. Increased oxidative stress is implicated in the pathogenesis of rheumatoid arthritis (RA). We undertook this study to investigate the impact of rebamipide on the development of arthritis and the pathophysiologic mechanisms by which rebamipide attenuates arthritis severity in a murine model of RA. Methods Collagen-induced arthritis (CIA) was induced in DBA/1J mice. Anti-type II collagen antibody titers and interleukin-17 (IL-17) levels were determined using enzyme-linked immunosorbent assay. The expression of transcription factors was analyzed by immunostaining and Western blotting. Frequencies of IL-17-producing CD4+ T cells (Th17 cells) and CD4+CD25+FoxP3+ Treg cells were analyzed by flow cytometry. Results Rebamipide reduced the clinical arthritis score and severity of histologic inflammation and cartilage destruction in a dose-dependent manner. The joints isolated from rebamipide-treated mice with CIA showed decreased expression of nitrotyrosine, an oxidative stress marker. Rebamipide-treated mice showed lower circulating levels of type II collagen-specific IgG, IgG1, and IgG2a. Whereas the number of Th17 cells in spleens was decreased in rebamipide-treated mice with CIA, a significant increase in the number of Treg cells in spleens was observed. In vitro, rebamipide inhibited Th17 cell differentiation through STAT-3/retinoic acid receptor-related orphan nuclear receptor γt and reciprocally induced Treg cell differentiation through FoxP3. Rebamipide increased Nrf2 nuclear activities in murine CD4+ T cells and LBRM-33 murine T lymphoma cells. Heme oxygenase 1 (HO-1) expression in the spleens was markedly increased in rebamipide-treated mice. Conclusion The inhibitory effects of rebamipide on joint inflammation are associated with recovery from an imbalance between Th17 cells and Treg cells and with activation of an Nrf2/HO-1 antioxidant pathway.
- Subjects
DRUG therapy for arthritis; GASTROINTESTINAL agents; REACTIVE oxygen species; ANALYSIS of variance; ANIMAL experimentation; ARTHRITIS; BIOLOGICAL models; CARTILAGE; CELL differentiation; DOSE-effect relationship in pharmacology; FLOW cytometry; GENE expression; IMMUNOHISTOCHEMISTRY; INTERLEUKINS; MICE; MICROSCOPY; POLYMERASE chain reaction; PROBABILITY theory; RESEARCH funding; STATISTICAL hypothesis testing; T-test (Statistics); SEVERITY of illness index; DATA analysis software; THERAPEUTICS
- Publication
Arthritis & Rheumatology, 2014, Vol 66, Issue 4, p874
- ISSN
2326-5191
- Publication type
Article
- DOI
10.1002/art.38310