| First Author | Deroide N | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 3 | Pages | 1176-81 |
| PubMed ID | 23454767 | Mgi Jnum | J:196376 |
| Mgi Id | MGI:5487855 | Doi | 10.1172/JCI65167 |
| Citation | Deroide N, et al. (2013) MFGE8 inhibits inflammasome-induced IL-1beta production and limits postischemic cerebral injury. J Clin Invest 123(3):1176-81 |
| abstractText | Milk fat globule-EGF 8 (MFGE8) plays important, nonredundant roles in several biological processes, including apoptotic cell clearance, angiogenesis, and adaptive immunity. Several recent studies have reported a potential role for MFGE8 in regulation of the innate immune response; however, the precise mechanisms underlying this role are poorly understood. Here, we show that MFGE8 is an endogenous inhibitor of inflammasome-induced IL-1beta production. MFGE8 inhibited necrotic cell-induced and ATP-dependent IL-1beta production by macrophages through mediation of integrin beta(3) and P2X7 receptor interactions in primed cells. Itgb3 deficiency in macrophages abrogated the inhibitory effect of MFGE8 on ATP-induced IL-1beta production. In a setting of postischemic cerebral injury in mice, MFGE8 deficiency was associated with enhanced IL-1beta production and larger infarct size; the latter was abolished after treatment with IL-1 receptor antagonist. MFGE8 supplementation significantly dampened caspase-1 activation and IL-1beta production and reduced infarct size in wild-type mice, but did not limit cerebral necrosis in Il1b-, Itgb3-, or P2rx7-deficient animals. In conclusion, we demonstrated that MFGE8 regulates innate immunity through inhibition of inflammasome-induced IL-1beta production. |
