https://scholars.lib.ntu.edu.tw/handle/123456789/196334
標題: | TLR-induced PAI-2 expression suppresses IL-1 beta processing via increasing autophagy and NLRP3 degradation | 作者: | Chuang, Shih-Yi Yang, Chih-Hsiang Chou, Chih-Chang Chiang, Yu-Ping Chuang, Tsung-Hsien Hsu, Li-Chung |
公開日期: | 2013 | 卷: | 110 | 期: | 40 | 起(迄)頁: | 16079-16084 | 來源出版物: | Proc. Natl. Acad. Sci. U. S. A. | 摘要: | The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, a multiprotein complex, triggers caspase-1 activation and maturation of the proinflammatory cytokines IL-1 beta and IL-18 upon sensing a wide range of pathogen-and damage-associated molecules. Dysregulation of NLRP3 inflammasome activity contributes to the pathogenesis of many diseases, but its regulation remains poorly defined. Here we show that depletion of plasminogen activator inhibitor type 2 (PAI-2), a serine protease inhibitor, resulted in NLRP3- and ASC (apoptosis-associated Speck-like protein containing a C-terminal caspase recruitment domain)dependent caspase-1 activation and IL-1 beta secretion in macrophages upon Toll-like receptor 2 (TLR2) and TLR4 engagement. TLR2 or TLR4 agonist induced PAI-2 expression, which subsequently stabilized the autophagic protein Beclin 1 to promote autophagy, resulting in decreases in mitochondrial reactive oxygen species, NLRP3 protein level, and pro-IL-1 beta processing. Likewise, overexpressing Beclin 1 in PAI-2-deficient cells rescued the suppression of NLRP3 activation in response to LPS. Together, our data identify a tier of TLR signaling in controlling NLRP3 inflammasome activation and reveal a cell-autonomous mechanism which inversely regulates TLR- or Escherichia coli-induced mitochondrial dysfunction, oxidative stress, and IL-1 beta-driven inflammation. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/259891 |
顯示於: | 醫學系 |
檔案 | 描述 | 大小 | 格式 | |
---|---|---|---|---|
index.html | 23.17 kB | HTML | 檢視/開啟 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。