IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis

Masanori Nakayama, Yasuo Niki, Toshiki Kawasaki, Yuki Takeda, Hiroyasu Ikegami, Yoshiaki Toyama, Takeshi Miyamoto

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Interleukin (IL)-32 is known to exert adujvant effects on innate immune response, however, receptors and downstream signaling pathways remain to be clarified. Here we found that IL-32γ upregulated serine protease activity of proteinase-3 (PR3), in turn triggering protease-activated receptor 2 (PAR2) signaling. Interestingly, silencing of PR3 or PAR2 using siRNA markedly diminished IL-32γ-induced TNFα and IFN-β mRNA expression. IL-32γ-PAR2 axis utilized TRIF and Ras-Raf-1 pathways. On stimulation with lipopolysaccharide (LPS), differential activation of protein kinase C isoforms modulated the balance between LPS-TLR4-TRIF and IL-32-PAR2-TRIF axes, because LPS was a strong inducer of IL-32γ. IL-32-PAR2-TRIF axis might serve not only as an extracellular sensor of bacterial and autologous proteases, but also as a modulator of innate and adaptive immunity during infection.

Original languageEnglish
Article number2960
JournalScientific reports
Volume3
DOIs
Publication statusPublished - 2013 Oct 16

ASJC Scopus subject areas

  • General

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