Document Detail


Mature interleukin-33 is produced by calpain-mediated cleavage in vivo.
MedLine Citation:
PMID:  19596270     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Interleukin (IL)-33 is a novel member of the IL-1 family. IL-33 is primarily synthesized as a 30-kDa precursor (pro-IL-33). Pro-IL-33 is cleaved by caspase-1 into an 18-kDa mature form (mature IL-33) in vitro. Recombinant mature IL-33 has been known to induce T-helper type-2 (Th2)-associated cytokines and inflammatory cytokines via its receptor, ST2L. However, processing of pro-IL-33 in vivo has not been clarified yet. Here, we report that calpain mediates pro-IL-33 processing in vivo. Pro-IL-33 was expressed by stimulating human epithelial cells with phorbol 12-myristate 13-acetate. Calcium ionophore induced pro-IL-33 cleavage and mature IL-33 production. This cleavage was inhibited by treatment with a calcium chelator and calpain inhibitors. Moreover, short interfering RNA-mediated knockdown of calpains suppressed pro-IL-33 cleavage. These results indicate that calpains play a critical role in pro-IL-33 processing in vivo.
Authors:
Morisada Hayakawa; Hiroko Hayakawa; Yasushi Matsuyama; Hiroyuki Tamemoto; Hitoaki Okazaki; Shin-ichi Tominaga
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-09
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  387     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-07-31     Completed Date:  2009-08-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  218-22     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, Japan. morisada@jichi.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Calcium / pharmacology
Calpain / genetics,  metabolism*
Cell Line, Tumor
Endothelial Cells / drug effects,  enzymology,  metabolism
Epithelial Cells / drug effects,  enzymology,  metabolism
Humans
Interleukins / metabolism*
RNA, Small Interfering / genetics
Tetradecanoylphorbol Acetate / pharmacology
Chemical
Reg. No./Substance:
0/IL33 protein, human; 0/Interleukins; 0/RNA, Small Interfering; 16561-29-8/Tetradecanoylphorbol Acetate; 7440-70-2/Calcium; EC 3.4.22.-/Calpain

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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