Mature interleukin-33 is produced by calpain-mediated cleavage in vivo.

Abstract:

: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

Hayakawa M,Hayakawa H,Matsuyama Y,Tamemoto H,Okazaki H,Tominaga S

doi

10.1016/j.bbrc.2009.07.018

subject

Has Abstract

pub_date

2009-09-11 00:00:00

pages

218-22

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(09)01357-6

journal_volume

387

pub_type

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