| First Author | Fettelschoss A | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 44 | Pages | 18055-60 |
| PubMed ID | 22006336 | Mgi Jnum | J:180059 |
| Mgi Id | MGI:5305357 | Doi | 10.1073/pnas.1109176108 |
| Citation | Fettelschoss A, et al. (2011) Inflammasome activation and IL-1beta target IL-1alpha for secretion as opposed to surface expression. Proc Natl Acad Sci U S A 108(44):18055-60 |
| abstractText | Interleukin-1alpha (IL-1alpha) and -beta both bind to the same IL-1 receptor (IL-1R) and are potent proinflammatory cytokines. Production of proinflammatory (pro)-IL-1alpha and pro-IL-1beta is induced by Toll-like receptor (TLR)-mediated NF-kappaB activation. Additional stimulus involving activation of the inflammasome and caspase-1 is required for proteolytic cleavage and secretion of mature IL-1beta. The regulation of IL-1alpha maturation and secretion, however, remains elusive. IL-1alpha exists as a cell surface-associated form and as a mature secreted form. Here we show that both forms of IL-1alpha, the surface and secreted form, are differentially regulated. Surface IL-1alpha requires NF-kappaB activation only, whereas secretion of mature IL-1alpha requires additional activation of the inflammasome and caspase-1. Surprisingly, secretion of IL-1alpha also required the presence of IL-1beta, as demonstrated in IL-1beta-deficient mice. We further demonstrate that IL-1beta directly binds IL-1alpha, thus identifying IL-1beta as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases. |
