Mature interleukin-33 is produced by calpain-mediated cleavage in vivo.
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.
Hayakawa
Morisada
M
Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi, Japan. morisada@jichi.ac.jp
Hayakawa
Hiroko
H
Matsuyama
Yasushi
Y
Tamemoto
Hiroyuki
H
Okazaki
Hitoaki
H
Tominaga
Shin-ichi
S
D002118:Calcium / Q000494:pharmacology; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D034741:RNA, Small Interfering; D002154:Calpain; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium