Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1?.

ABSTRACT: Granzyme B is a cytotoxic lymphocyte-derived protease that plays a central role in promoting apoptosis of virus-infected target cells, through direct proteolysis and activation of constituents of the cell death machinery. However, previous studies have also implicated granzymes A and B in the production of proinflammatory cytokines, via a mechanism that remains undefined. Here we show that IL-1? is a substrate for granzyme B and that proteolysis potently enhanced the biological activity of this cytokine in vitro as well as in vivo. Consistent with this, compared with full-length IL-1?, granzyme B-processed IL-1? exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1? within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1? processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.

SUBMITTER: Afonina IS 

PROVIDER: S-EPMC3319689 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature