ASC plays a role in the priming phase of the immune response to type II collagen in collagen-induced arthritis
ASC plays a role in the priming phase of the immune response to type II collagen in collagen-induced arthritis
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DOI：
10.1007/s00296-011-1825-y
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发表时间：
2012-06
影响因子：
4
通讯作者：
H. Yamazaki;M. Takeoka;M. Kitazawa;T. Ehara;N. Itano;H. Kato;S. Taniguchi
中科院分区：
文献类型：
--
作者：
H. Yamazaki;M. Takeoka;M. Kitazawa;T. Ehara;N. Itano;H. Kato;S. Taniguchi
虽然类风湿性关节炎(RA)是一种病因不明的自身免疫性疾病，但IL-1β和IL-18在RA的病理生理机制中的作用已被证实。IL-1β和IL-18是在含有Caspase Recruit结构域(Asc)的凋亡相关SPECK样蛋白存在的情况下通过切割其前体产生的，Asc是一种已知的激活Proaspase-1的接头蛋白。因此，我们利用Asc缺陷(Asc−/−)和野生型(Asc+/+)小鼠研究了Asc在小鼠胶原诱导性关节炎(CIA)和胶原抗体诱导性关节炎(CAIA)的进展中的作用。组织采用免疫组织化学方法进行分析，血清采用ELISA法进行分析。我们观察到Asc在CIA DBA小鼠关节中的表达增加，以及IL-1β和IL-18的表达，这表明Asc参与了疾病的发生发展。接下来，我们证明了与asc−/−小鼠相比，asc+/+小鼠CIA膝关节中炎症细胞的渗透和软骨/骨的破坏显著增加。在Asc+/+和Asc−/−CAIA小鼠中没有发现这种差异。在膝关节细胞因子的表达方面，与野生型小鼠相比，Asc缺陷的CIA小鼠的IL-1β和IL-18的表达受到抑制，但在两组小鼠的CaA关节中的表达相似。综上所述，我们可以得出结论，ASC参与了CIA的发展，并在II型胶原免疫反应的启动阶段发挥了作用。
Although rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology, the role of IL-1β and IL-18 in the pathophysiology of RA has been well established. IL-1β and IL-18 are generated via cleavage of their pro-forms in the presence of the apoptosis-associated speck-like protein containing a caspase recruit domain (ASC), a known adaptor protein that activates procaspase-1. As such, we investigated the involvement of ASC in the progression of murine collagen-induced arthritis (CIA) and collagen antibody-induced arthritis (CAIA) using ASC-deficient (ASC−/−) and wild-type (ASC+/+) mice. Analyses were performed by immunohistochemistry for tissues and ELISA for sera. We observed an increase in the expression of ASC, as well as IL-1β and IL-18, in the joints of CIA DBA mice, which indicated that ASC is involved in disease development. Next, we demonstrated that the infiltration of inflammatory cells and cartilage/bone destruction in CIA knee joints were significantly increased in ASC+/+mice compared with ASC−/−mice. No such differences were noted in ASC+/+and ASC−/−CAIA mice. In terms of cytokine expression in knee joints, IL-1β and IL-18 were depressed in ASC-deficient CIA mice compared with wild-type mice, but were similarly expressed in CAIA joints in both mice groups. Taken together, we can conclude that ASC is involved in the development of CIA and plays a role in the priming phase of the immune response to type II collagen.