title: Integrin α5β1 activates the NLRP3 inflammasome by direct interaction with a bacterial surface protein.
abstract: 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.
authors.affiliation: Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hye-Kyoung
authors.initials: HK
authors.lastname: Jun
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Hae-Ri
authors.initials: HR
authors.lastname: Lee
authors.forename: Bong-Kyu
authors.initials: BK
authors.lastname: Choi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011188:Potassium / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D048373:Treponema denticola / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D058847:Inflammasomes; D039081:Integrin alpha5beta1; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate; D020170:Caspase 1; D011188:Potassium