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

Hdl Handle:
http://hdl.handle.net/10147/229931
Title:
Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.
Authors:
Afonina, Inna S; Tynan, Graham A; Logue, Susan E; Cullen, Sean P; Bots, Michael; Lüthi, Alexander U; Reeves, Emer P; McElvaney, Noel G; Medema, Jan P; Lavelle, Ed C; Martin, Seamus J
Affiliation:
Molecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.
Citation:
Granzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α. 2011, 44 (2):265-78 Mol. Cell
Journal:
Molecular cell
Issue Date:
21-Oct-2011
URI:
http://hdl.handle.net/10147/229931
DOI:
10.1016/j.molcel.2011.07.037
PubMed ID:
22017873
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319689/pdf/ukmss-47203.pdf
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-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.
Item Type:
Article
Language:
en
MeSH:
Animals; Cytokines; Granzymes; HeLa Cells; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Interleukin-1alpha; Mice; Mice, Inbred BALB C; Proteolysis
ISSN:
1097-4164

Full metadata record

DC FieldValue Language
dc.contributor.authorAfonina, Inna Sen_GB
dc.contributor.authorTynan, Graham Aen_GB
dc.contributor.authorLogue, Susan Een_GB
dc.contributor.authorCullen, Sean Pen_GB
dc.contributor.authorBots, Michaelen_GB
dc.contributor.authorLüthi, Alexander Uen_GB
dc.contributor.authorReeves, Emer Pen_GB
dc.contributor.authorMcElvaney, Noel Gen_GB
dc.contributor.authorMedema, Jan Pen_GB
dc.contributor.authorLavelle, Ed Cen_GB
dc.contributor.authorMartin, Seamus Jen_GB
dc.date.accessioned2012-06-20T14:05:10Z-
dc.date.available2012-06-20T14:05:10Z-
dc.date.issued2011-10-21-
dc.identifier.citationGranzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α. 2011, 44 (2):265-78 Mol. Cellen_GB
dc.identifier.issn1097-4164-
dc.identifier.pmid22017873-
dc.identifier.doi10.1016/j.molcel.2011.07.037-
dc.identifier.urihttp://hdl.handle.net/10147/229931-
dc.description.abstractGranzyme 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.en_GB
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319689/pdf/ukmss-47203.pdfen_GB
dc.rightsArchived with thanks to Molecular cellen_GB
dc.subject.meshAnimals-
dc.subject.meshCytokines-
dc.subject.meshGranzymes-
dc.subject.meshHeLa Cells-
dc.subject.meshHuman Umbilical Vein Endothelial Cells-
dc.subject.meshHumans-
dc.subject.meshInflammation-
dc.subject.meshInterleukin-1alpha-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshProteolysis-
dc.titleGranzyme B-dependent proteolysis acts as a switch to enhance the proinflammatory activity of IL-1α.en_GB
dc.typeArticleen
dc.contributor.departmentMolecular Cell Biology Laboratory, Department of Genetics, The Smurfit Institute, Trinity College, Dublin 2, Ireland.en_GB
dc.identifier.journalMolecular cellen_GB
dc.description.provinceLeinsteren

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