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

25 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
Pages (from-to)2960
Number of pages1
JournalScientific Reports
Volume3
Publication statusPublished - 2013

Fingerprint

PAR-2 Receptor
Interleukins
Innate Immunity
Lipopolysaccharides
Myeloblastin
Serine Proteases
Adaptive Immunity
Protein Kinase C
Small Interfering RNA
Protein Isoforms
Peptide Hydrolases
Messenger RNA
Infection

ASJC Scopus subject areas

  • General

Cite this

Nakayama, M., Niki, Y., Kawasaki, T., Takeda, Y., Ikegami, H., Toyama, Y., & Miyamoto, T. (2013). IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis. Scientific Reports, 3, 2960.

IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis. / Nakayama, Masanori; Niki, Yasuo; Kawasaki, Toshiki; Takeda, Yuki; Ikegami, Hiroyasu; Toyama, Yoshiaki; Miyamoto, Takeshi.

In: Scientific Reports, Vol. 3, 2013, p. 2960.

Research output: Contribution to journalArticle

Nakayama, M, Niki, Y, Kawasaki, T, Takeda, Y, Ikegami, H, Toyama, Y & Miyamoto, T 2013, 'IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis.', Scientific Reports, vol. 3, pp. 2960.
Nakayama, Masanori ; Niki, Yasuo ; Kawasaki, Toshiki ; Takeda, Yuki ; Ikegami, Hiroyasu ; Toyama, Yoshiaki ; Miyamoto, Takeshi. / IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis. In: Scientific Reports. 2013 ; Vol. 3. pp. 2960.
@article{341abeb3903844ccbe4570aba35553a9,
title = "IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis.",
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.",
author = "Masanori Nakayama and Yasuo Niki and Toshiki Kawasaki and Yuki Takeda and Hiroyasu Ikegami and Yoshiaki Toyama and Takeshi Miyamoto",
year = "2013",
language = "English",
volume = "3",
pages = "2960",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis.

AU - Nakayama, Masanori

AU - Niki, Yasuo

AU - Kawasaki, Toshiki

AU - Takeda, Yuki

AU - Ikegami, Hiroyasu

AU - Toyama, Yoshiaki

AU - Miyamoto, Takeshi

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84902282010&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902282010&partnerID=8YFLogxK

M3 - Article

C2 - 24129891

AN - SCOPUS:84902282010

VL - 3

SP - 2960

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

ER -