ASC plays a role in the IL-1beta, IL-18 pathway of the immune response to type II collagen in collagen-induced arthritis

ASC 在胶原诱导性关节炎中对 II 型胶原免疫反应的 IL-1beta、IL-18 通路中发挥作用

• 批准号: 21591939
• 负责人: TAKEOKA Michiko
• 金额: $ 2.25万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591939/
• 关键词: リウマチ病学; ASC; 関節炎; IL-1beta; IL-18; DBAマウス; コラーゲン誘発関節炎

We investigated the involvement of apoptosis-associated speck-like protein containing a caspase recruit domain(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.

我们利用ASC缺陷型（ASC-/-）和野生型（ASC+/+）小鼠研究了含有caspase募集结构域（ASC）的凋亡相关斑点样蛋白在小鼠胶原诱导关节炎（CIA）和胶原抗体诱导关节炎（CAIA）进展中的作用。组织免疫组化、血清ELISA分析。我们观察到ASC和IL-1β的表达增加。和IL-18，这表明ASC参与了疾病的发展。接下来，我们证明了与ASC-/-小鼠相比，ASC+/+小鼠的炎症细胞浸润和CIA膝关节软骨/骨破坏明显增加。在ASC+/+和ASC-/- caia小鼠中没有发现这种差异。在膝关节细胞因子表达方面，IL-1β。和IL-18在asc缺失的CIA小鼠中与野生型小鼠相比表达较低，但在两组小鼠的CAIA关节中表达相似。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作用。

项目成果

ASC Deleted Mice Are Resistant to Collagen-Induced Arthritis.

ASC 缺失小鼠对胶原蛋白诱导的关节炎具有抵抗力。

• 发表时间: 2009
• 作者: Yamazaki H;Takeoka M;Ehara T;Itano N;Kato H;Taniguchi S.
• 通讯作者: Taniguchi S.

ASC plays a role in the priming phase of the immune response to type II collagen in collagen-induced arthritis

• DOI: 10.1007/s00296-011-1825-y
• 发表时间: 2012-06
• 期刊: Rheumatology International
• 影响因子: 4
• 作者: H. Yamazaki;M. Takeoka;M. Kitazawa;T. Ehara;N. Itano;H. Kato;S. Taniguchi

コラーゲン誘発関節炎におけるアポトーシス制御蛋白ASCの役割

凋亡控制蛋白ASC在胶原诱导的关节炎中的作用

• 发表时间: 2010
• 作者: 山崎秀;加藤博之
• 通讯作者: 加藤博之