IL-38: A new factor in rheumatoid arthritis Shin-Ichi Takenaka 1 , Shinjiro Kaieda 1 , Tomotaka Kawayama 1 , Masanobu Matsuoka 1 , Yoichiro Kaku 1 , Takashi Kinoshita 1 , Yuki Sakazaki 1 , Masaki Okamoto 1 , Masaki Tominaga 1 , Katsuya Kanesaki 2 , Asako Chiba 3 , Sachiko Miyake 3 , Hiroaki Ida 1 , Tomoaki Hoshino Biochem Biophys Rep
4
386-391
2015
Show Abstract
The newly characterized cytokine IL-38 (IL-1F10) belongs to the IL-1 family of cytokines. Previous work has demonstrated that IL-38 inhibited Candida albicans-induced IL-17 production from peripheral blood mononuclear cells. However, it is still unclear whether IL-38 is an inflammatory or an anti-inflammatory cytokine. We generated anti-human IL-38 monoclonal antibodies in order to perform immunohistochemical staining and an enzyme-linked immunosorbent assay. While human recombinant IL-38 protein was not cleaved by recombinant caspase-1, chymase, or PR3 in vitro, overexpression of IL-38 cDNA produced a soluble form of IL-38 protein. Furthermore, immunohistochemical analysis showed that synovial tissues obtained from RA patients strongly expressed IL-38 protein. To investigate the biological role of IL-38, C57BL/6 IL-38 gene-deficient (-/-) mice were used in an autoantibody-induced rheumatoid arthritis (RA) mouse model. As compared with control mice, IL-38 (-/-) mice showed greater disease severity, accompanied by higher IL-1β and IL-6 gene expression in the joints. Therefore, IL-38 acts as an inhibitor of the pathogenesis of autoantibody-induced arthritis in mice and may have a role in the development or progression of RA in humans. | 29124228
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