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

Mol Cell. 2011 Oct 21;44(2):265-78. doi: 10.1016/j.molcel.2011.07.037.


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-1α 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-1α, granzyme B-processed IL-1α exhibited more potent activity as an immunoadjuvant in vivo. Furthermore, proteolysis of IL-1α within the same region, by proteases such as calpain and elastase, was also found to enhance its biological potency. Thus, IL-1α processing by multiple immune-related proteases, including granzyme B, acts as a switch to enhance the proinflammatory properties of this cytokine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / immunology
  • Cytokines / metabolism
  • Granzymes / metabolism*
  • HeLa Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-1alpha / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Proteolysis


  • Cytokines
  • Interleukin-1alpha
  • Granzymes