IL-38: A new factor in rheumatoid arthritis.
IL-38: A new factor in rheumatoid arthritis.
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DOI：
10.1016/j.bbrep.2015.10.015
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发表时间：
2015-12
影响因子：
2.7
通讯作者：
Hoshino T
中科院分区：
文献类型：
--
作者：
Takenaka SI;Kaieda S;Kawayama T;Matsuoka M;Kaku Y;Kinoshita T;Sakazaki Y;Okamoto M;Tominaga M;Kanesaki K;Chiba A;Miyake S;Ida H;Hoshino T
新鉴定的细胞因子IL-38（IL-1F 10）属于细胞因子IL-1家族。先前的工作已经证明IL-38抑制白色念珠菌诱导的外周血单核细胞产生IL-17。然而，目前还不清楚IL-38是炎症还是抗炎细胞因子。我们产生了抗人IL-38单克隆抗体，以进行免疫组织化学染色和酶联免疫吸附试验。虽然人重组IL-38蛋白在体外不被重组半胱天冬酶-1、糜蛋白酶或PR 3切割，但IL-38 cDNA的过表达产生可溶形式的IL-38蛋白。此外，免疫组化分析显示，从RA患者获得的滑膜组织强烈表达IL-38蛋白。为了研究IL-38的生物学作用，在自身抗体诱导的类风湿性关节炎（RA）小鼠模型中使用C57 BL/6 IL-38基因缺陷（-/-）小鼠。与对照组小鼠相比，IL-38（−/−）小鼠表现出更严重的疾病，伴随着关节中更高的IL-1β和IL-6基因表达。因此，IL-38在小鼠中作为自身抗体诱导的关节炎的发病机制的抑制剂，并且可能在人类RA的发展或进展中起作用。在从RA患者获得的血清中检测到可溶性形式的IL-38。IL-38蛋白在RA滑膜组织中呈高表达。IL-38的表达在mRNA水平上在小鼠关节炎期间上调。IL-38可以通过抑制IL-1诱导的炎症来减轻关节炎症。
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. The soluble form of IL-38 is detected in the sera obtained from of RA patients. IL-38 protein was highly expressed in the synovial lining of RA synovium. IL-38 expression was up-regulated during arthritis in mice at the mRNA level. IL-38 may attenuate joint inflammation by inhibiting the IL-1 induced inflammation.