Integrin α5ß1 activates the NLRP3 inflammasome by direct interaction with a bacterial surface protein.
Immunity
; 36(5): 755-68, 2012 May 25.
Article
in En
| MEDLINE
| ID: mdl-22608495
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 α5ß1 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 α5ß1 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 α5ß1 antibody and oxATP, an ATP receptor antagonist, inhibited NLRP3 expression, caspase-1 activation, interleukin-1ß (IL-1ß) secretion, and proIL-1ß synthesis, all of which were regulated by NF-κB activation. Therefore, our data has identified the integrin α5ß1 as a principal cell membrane receptor for both NLRP3 inflammasome activation and IL-1ß transcription by a bacterial protein, which could exaggerate inflammation, a characteristic of periodontitis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacterial Outer Membrane Proteins
/
Carrier Proteins
/
Integrin alpha5beta1
/
Inflammasomes
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2012
Document type:
Article