PMID- 22017873
OWN - NLM
STAT- MEDLINE
DCOM- 20111230
LR  - 20220309
IS  - 1097-4164 (Electronic)
IS  - 1097-2765 (Print)
IS  - 1097-2765 (Linking)
VI  - 44
IP  - 2
DP  - 2011 Oct 21
TI  - Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory 
      activity of IL-1alpha.
PG  - 265-78
LID - 10.1016/j.molcel.2011.07.037 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Afonina, Inna S
AU  - Afonina IS
AD  - Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, 
      Trinity College, Dublin 2, Ireland.
FAU - Tynan, Graham A
AU  - Tynan GA
FAU - Logue, Susan E
AU  - Logue SE
FAU - Cullen, Sean P
AU  - Cullen SP
FAU - Bots, Michael
AU  - Bots M
FAU - Luthi, Alexander U
AU  - Luthi AU
FAU - Reeves, Emer P
AU  - Reeves EP
FAU - McElvaney, Noel G
AU  - McElvaney NG
FAU - Medema, Jan P
AU  - Medema JP
FAU - Lavelle, Ed C
AU  - Lavelle EC
FAU - Martin, Seamus J
AU  - Martin SJ
LA  - eng
GR  - 082749/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell
JT  - Molecular cell
JID - 9802571
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1alpha)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Animals
MH  - Cytokines/immunology/metabolism
MH  - Granzymes/*metabolism
MH  - HeLa Cells
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Inflammation/immunology/metabolism
MH  - Interleukin-1alpha/*metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Proteolysis
PMC - PMC3319689
MID - UKMS47203
OID - NLM: UKMS47203
EDAT- 2011/10/25 06:00
MHDA- 2011/12/31 06:00
PMCR- 2012/04/04
CRDT- 2011/10/25 06:00
PHST- 2010/09/01 00:00 [received]
PHST- 2011/06/17 00:00 [revised]
PHST- 2011/07/15 00:00 [accepted]
PHST- 2011/10/25 06:00 [entrez]
PHST- 2011/10/25 06:00 [pubmed]
PHST- 2011/12/31 06:00 [medline]
PHST- 2012/04/04 00:00 [pmc-release]
AID - S1097-2765(11)00717-9 [pii]
AID - 10.1016/j.molcel.2011.07.037 [doi]
PST - ppublish
SO  - Mol Cell. 2011 Oct 21;44(2):265-78. doi: 10.1016/j.molcel.2011.07.037.