Granzyme B-dependent proteolysis acts as a switch to enhance the pro-inflammatory activity of IL-1
Citation:
Afonina, I.S., Tynan, G.A., Logue, S. E., Cullen, S.P., Bots, M., Lüthi, A.U., Reeves, E.P., McElvaney, N.G., Medema, J.P., Lavelle, E.C. and Martin, S.J., Granzyme B-dependent proteolysis acts as a switch to enhance the pro-inflammatory activity of IL-1, Molecular Cell, 44, 2, 2011, 465 - 478Download Item:
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 pro-inflammatory 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 pro-inflammatory properties of this cytokine.
Sponsor
Grant Number
Science Foundation Ireland (SFI)
SFI Strategic Research Cluster Grant
Author's Homepage:
http://people.tcd.ie/lavelleehttp://people.tcd.ie/martinsj
Description:
PUBLISHED
Author: LAVELLE, EDWARD; MARTIN, SEAMUS
Type of material:
Journal ArticleCollections
Series/Report no:
Molecular Cell44
2
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Full text availableKeywords:
Granzyme BSubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1016/j.molcel.2011.07.037Metadata
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