| First Author | Afonina IS | Year | 2011 |
| Journal | Mol Cell | Volume | 44 |
| Issue | 2 | Pages | 265-78 |
| PubMed ID | 22017873 | Mgi Jnum | J:180695 |
| Mgi Id | MGI:5306855 | Doi | 10.1016/j.molcel.2011.07.037 |
| Citation | Afonina IS, et al. (2011) Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1alpha. Mol Cell 44(2):265-78 |
| abstractText | 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-1alpha 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-1alpha, granzyme B-processed IL-1alpha exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1alpha within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1alpha processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine. |
