近日，来自首尔大学的研究人员发现，整合素α5β1通过与一种细菌表面蛋白Td92的直接相互作用，激活了NLRP3炎症小体。相关研究成果于5月17日在线发表在Immunity上。
整合素是细胞表面的一种异二聚体糖蛋白，由α及β两种亚单位组成，介导了细胞与细胞，细胞与细胞外基质，以及细胞与病原体之间的相互作用。
Td92是齿垢密螺旋体的外膜蛋白，能够诱导破骨细胞的生成及扩大炎症作用。在这项研究里，Bong-Kyu Cho等人发现，在由Td92刺激的巨噬细胞中，整合素α5β1激活了NLRP3炎症小体。
进一步研究发现，Td92与细胞膜整合素α5β1的直接相互作用会导致ATP释放及K+外流，而且这些都是NLRP3激活的主要事件。研究发现，这种相互作用不依赖精氨酸-甘氨酸-天冬氨酸（RGD）结构，而且Td92的内化也不需要于这种激活作用。
整合素α5β1抗体及ATP受体拮抗剂OxATP（氧化型ATP），能够抑制NLRP3的表达、caspase-1的激活、IL-1β的分泌以及proIL-1β的合成，所有的这些都被NF-κB的激活所调节。
Bong-Kyu Cho表示，该研究表明，整合素α5β1作为一个主要的细胞膜受体，在与细菌表面蛋白Td92相互作用后，促进了NLRP3炎症小体的激活及IL-1β的转录。（生物谷Deepblue编译）
doi: 10.1016/j.immuni.2012.05.002
PMC:
PMID:
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.
