Inflammasome-independent regulation of IL-1-family cytokines.

Annu Rev Immunol 2015 10;33:49-77. Epub 2014 Dec 10.

Department of Internal Medicine.

Induction, production, and release of proinflammatory cytokines are essential steps to establish an effective host defense. Cytokines of the interleukin-1 (IL-1) family induce inflammation and regulate T lymphocyte responses while also displaying homeostatic and metabolic activities. With the exception of the IL-1 receptor antagonist, all IL-1 family cytokines lack a signal peptide and require proteolytic processing into an active molecule. One such unique protease is caspase-1, which is activated by protein platforms called the inflammasomes. However, increasing evidence suggests that inflammasomes and caspase-1 are not the only mechanism for processing IL-1 cytokines. IL-1 cytokines are often released as precursors and require extracellular processing for activity. Here we review the inflammasome-independent enzymatic processes that are able to activate IL-1 cytokines, paying special attention to neutrophil-derived serine proteases, which subsequently induce inflammation and modulate host defense. The inflammasome-independent processing of IL-1 cytokines has important consequences for understanding inflammatory diseases, and it impacts the design of IL-1-based modulatory therapies.

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-immunol-032414-112306DOI Listing
December 2015
96 Reads

Publication Analysis

Top Keywords

il-1 cytokines
16
processing il-1
8
il-1 family
8
induce inflammation
8
host defense
8
cytokines
8
il-1
7
caspase-1 mechanism
4
inflammasomes caspase-1
4
suggests inflammasomes
4
require extracellular
4
mechanism processing
4
precursors require
4
evidence suggests
4
cytokines il-1
4
released precursors
4
cytokines released
4
inflammasomes increasing
4
proteolytic processing
4
processing active
4

Similar Publications