Integrin 伪5尾1 Activates the NLRP3 Inflammasome by Direct Interaction with a Bacterial Surface Protein
- 作者：Hye-Kyoung Jun
- 刊名：Immunity
- 出版年：2012
- 期刊代码：40_10747613
- 类别：imm
- 出版时间：25 May, 2012
- 卷：36
- 期：5
- 页码：755-768
- 文件大小：1753 K
摘要
| Figures/TablesFigures/Tables | ReferencesReferences<h3 class="h3">Summaryh3>Integrins are cell-surface heterodimeric glycoproteins composed of alpha and beta subunits that mediate cell-cell, cell-extracellular matrix, and cell-pathogen interactions. In this study, we report a specific role of integrin 伪5尾1 in NLRP3 inflammasome activation in macrophages stimulated by Td92, a surface protein of the periodontopathogen, Treponema denticola. The direct interaction of Td92 with the cell membrane integrin 伪5尾1 resulted in ATP release and Kp>+ p> efflux, which are the main events in NLRP3 activation. This interaction was arginine-glycine-aspartate (RGD)-independent, and Td92 internalization was not required for the activity. An integrin 伪5尾1 antibody and oxATP, an ATP receptor antagonist, inhibited NLRP3 expression, caspase-1 activation, interleukin-1尾 (IL-1尾) secretion, and proIL-1尾 synthesis, all of which were regulated by NF-魏B activation. Therefore, our data has identified the integrin 伪5尾1 as a principal cell membrane receptor for both NLRP3 inflammasome activation and IL-1尾 transcription by a bacterial protein, which could exaggerate inflammation, a characteristic of periodontitis.