近日,，來自首爾大學的研究人員發(fā)現(xiàn)，整合素α5β1通過與一種細菌表面蛋白Td92的直接相互作用，激活了NLRP3炎癥小體。相關研究成果于5月17日在線發(fā)表在Immunity上,。
整合素是細胞表面的一種異二聚體糖蛋白，由α及β兩種亞單位組成,，介導了細胞與細胞,，細胞與細胞外基質，以及細胞與病原體之間的相互作用,。
Td92是齒垢密螺旋體的外膜蛋白,，能夠誘導破骨細胞的生成及擴大炎癥作用。在這項研究里,，Bong-Kyu Cho等人發(fā)現(xiàn),，在由Td92刺激的巨噬細胞中，整合素α5β1激活了NLRP3炎癥小體,。
進一步研究發(fā)現(xiàn)，Td92與細胞膜整合素α5β1的直接相互作用會導致ATP釋放及K+外流,，而且這些都是NLRP3激活的主要事件,。研究發(fā)現(xiàn)，這種相互作用不依賴精氨酸-甘氨酸-天冬氨酸（RGD）結構,，而且Td92的內化也不需要于這種激活作用,。
整合素α5β1抗體及ATP受體拮抗劑OxATP（氧化型ATP），能夠抑制NLRP3的表達,、caspase-1的激活,、IL-1β的分泌以及proIL-1β的合成，所有的這些都被NF-κB的激活所調節(jié),。
Bong-Kyu Cho表示,，該研究表明，整合素α5β1作為一個主要的細胞膜受體，在與細菌表面蛋白Td92相互作用后,，促進了NLRP3炎癥小體的激活及IL-1β的轉錄,。（生物谷Deepblue編譯）
doi: 10.1016/j.immuni.2012.05.002
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Integrin α5β1 Activates the NLRP3 Inflammasome by Direct Interaction with a Bacterial Surface Protein
Hye-Kyoung Jun, Sung-Hoon Lee, Hae-Ri Lee, Bong-Kyu Cho.
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 α5β1 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 α5β1 resulted in ATP release and K+ 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 α5β1 antibody and oxATP, an ATP receptor antagonist, inhibited NLRP3 expression, caspase-1 activation, interleukin-1β (IL-1β) secretion, and proIL-1β synthesis, all of which were regulated by NF-κB activation.Therefore, our data has identified the integrin α5β1 as a principal cell membrane receptor for both NLRP3 inflammasome activation and IL-1β transcription by a bacterial protein, which could exaggerate inflammation, a characteristic of periodontitis.
