IL-1 beta -converting enzyme (caspase-1) in intestinal inflammation.

Details

Serval ID
serval:BIB_193A15595BDB
Type
Article: article from journal or magazin.
Collection
Publications
Title
IL-1 beta -converting enzyme (caspase-1) in intestinal inflammation.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Siegmund B., Lehr H.A., Fantuzzi G., Dinarello C.A.
ISSN
0027-8424 (Print)
ISSN-L
0027-8424
Publication state
Published
Issued date
2001
Volume
98
Number
23
Pages
13249-13254
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.Publication Status: ppublish
Abstract
IL-1 beta-converting enzyme (ICE; caspase-1) is the intracellular protease that cleaves the precursors of IL-1 beta and IL-18 into active cytokines. In the present study, the effect of ICE deficiency was evaluated during experimental colitis in mice. In acute dextran sulfate sodium-induced colitis, ICE-deficient (ICE KO) mice exhibited a greater than 50% decrease of the clinical scores weight loss, diarrhea, rectal bleeding, and colon length, whereas daily treatment with IL-1 receptor antagonist revealed a modest reduction in colitis severity. To further characterize the function of ICE and its role in intestinal inflammation, chronic colitis was induced over a 30-day time period. During this chronic time course, ICE KO mice exhibited a near complete protection, as reflected by significantly reduced clinical scores and almost absent histological signs of colitis. Consistently, colon shortening occurred only in dextran sulfate sodium-exposed wild-type mice but not in ICE KO mice. Protection was accompanied by reduced spontaneous release of the proinflammatory cytokines IL-18, IL-1 beta, and IFN-gamma from total colon cultures. In addition, flow cytometric analysis of isolated mesenteric lymph node cells revealed evidence of reduced cell activation in ICE KO mice as evaluated by surface expression of CD3 CD69 and CD4 CD25. We conclude that inhibition of ICE represents a novel anti-inflammatory strategy for intestinal inflammation.
Keywords
Animals, Antigens, CD/metabolism, Caspase 1/genetics, Caspase 1/metabolism, Colitis/enzymology, Inflammation Mediators/metabolism, Interleukin-1/biosynthesis, Interleukin-18/biosynthesis, Mice, Mice, Knockout
Pubmed
Open Access
Yes
Create date
26/11/2011 13:43
Last modification date
20/08/2019 12:49
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