Inflammasome activation and IL-1? target IL-1? for secretion as opposed to surface expression.

ABSTRACT: Interleukin-1? (IL-1?) and -? both bind to the same IL-1 receptor (IL-1R) and are potent proinflammatory cytokines. Production of proinflammatory (pro)-IL-1? and pro-IL-1? is induced by Toll-like receptor (TLR)-mediated NF-?B activation. Additional stimulus involving activation of the inflammasome and caspase-1 is required for proteolytic cleavage and secretion of mature IL-1?. The regulation of IL-1? maturation and secretion, however, remains elusive. IL-1? exists as a cell surface-associated form and as a mature secreted form. Here we show that both forms of IL-1?, the surface and secreted form, are differentially regulated. Surface IL-1? requires NF-?B activation only, whereas secretion of mature IL-1? requires additional activation of the inflammasome and caspase-1. Surprisingly, secretion of IL-1? also required the presence of IL-1?, as demonstrated in IL-1?-deficient mice. We further demonstrate that IL-1? directly binds IL-1?, thus identifying IL-1? as a shuttle for another proinflammatory cytokine. These results have direct impact on selective treatment modalities of inflammatory diseases.

SUBMITTER: Fettelschoss A 

PROVIDER: S-EPMC3207698 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature