Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1.

Details

Serval ID
serval:BIB_516E98AB6ED9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inflammasome activators induce interleukin-1α secretion via distinct pathways with differential requirement for the protease function of caspase-1.
Journal
Immunity
Author(s)
Gross O., Yazdi A.S., Thomas C.J., Masin M., Heinz L.X., Guarda G., Quadroni M., Drexler S.K., Tschopp J.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
2012
Volume
36
Number
3
Pages
388-400
Language
english
Abstract
Through their capacity to sense danger signals and to generate active interleukin-1β (IL-1β), inflammasomes occupy a central role in the inflammatory response. In contrast to IL-1β, little is known about how IL-1α is regulated. We found that all inflammasome activators also induced the secretion of IL-1α, leading to the cosecretion of both IL-1 cytokines. Depending on the type of inflammasome activator, release of IL-1α was inflammasome dependent or independent. Calcium influx induced by the opening of cation channels was sufficient for the inflammasome-independent IL-1α secretion. In both cases, IL-1α was released primarily in a processed form, resulting from intracellular cleavage by calpain-like proteases. Inflammasome-caspase-1-dependent release of IL-1α and IL-1β was independent of caspase-1 catalytic activity, defining a mode of action for caspase-1. Because inflammasomes contribute to the pathology of numerous chronic inflammatory diseases such as gout and diabetes, IL-1α antagonists may be beneficial in the treatment of these disorders.
Keywords
Adaptor Proteins, Signal Transducing/metabolism, Animals, Apoptosis Regulatory Proteins/metabolism, Calcium Channels/metabolism, Calcium Signaling/immunology, Calcium-Binding Proteins/metabolism, Caspase 1/metabolism, Cell Death/immunology, Female, Humans, Inflammasomes/immunology, Inflammasomes/metabolism, Interleukin-1alpha/antagonists & inhibitors, Interleukin-1alpha/biosynthesis, Interleukin-1beta/biosynthesis, Male, Mice, Mice, 129 Strain, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins/metabolism, Peritonitis/immunology, Protein Processing, Post-Translational, Receptors, Interleukin-1/metabolism, Signal Transduction/immunology
Pubmed
Web of science
Open Access
Yes
Create date
03/05/2012 15:18
Last modification date
20/08/2019 14:07
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