Serratia marcescens serralysin induces inflammatory responses through protease-activated receptor 2

Yutaka Kida, Hiroyoshi Inoue, Takashi Shimizu, Koichi Kuwano

Research output: Contribution to journalArticle

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Abstract

The Serratia marcescens-derived protease serralysin is considered to play an important role in the pathogenesis of infection. Protease-activated receptor 2 (PAR-2) is activated by trypsin and also several other trypsin-like serine proteases, leading to the modulation of inflammatory and immune responses. However, little is known about the activation of PAR-2 by bacterial proteases and its roles in bacterial infection. In this study, we investigated whether S. marcescens serralysin activates host inflammatory responses through PAR-2. Our results demonstrated that serralysin induces interleukin-6 (IL-6) and IL-8 mRNA expression in a human lung squamous cell carcinoma, EBC-1 cells. In addition, serralysin activated activator protein 1 (AP-1)-, CCAAT/enhancer-binding protein (C/EBP)-, and nuclear factor-κB (NF-κB)-driven promoters in EBC-1 cells. An electrophoretic mobility shift assay showed that serralysin activates the binding of AP-1, C/EBPβ, and NF-κB in the cells. Inactivation of serralysin resulted in the failure of transactivation of AP-1-, C/EBP-, and NF-κB-driven promoters in the cells. Furthermore, serralysin activated AP-1-, C/EBP-, and NF-κB-driven promoters via PAR-2 in HeLa cells. PAR-2 antagonist peptides decreased serralysin-induced transactivation of AP-1-, C/EBP-, and NF-κB-driven promoters in EBC-1 cells. Considered together, these results suggest that serralysin requires PAR-2 to activate the critical transcription factors AP-1, C/EBPβ, and NF-κB for host inflammatory responses.

Original languageEnglish
Pages (from-to)164-174
Number of pages11
JournalInfection and Immunity
Volume75
Issue number1
DOIs
Publication statusPublished - 2007 Jan
Externally publishedYes

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serralysin
PAR-2 Receptor
Serratia marcescens
CCAAT-Enhancer-Binding Proteins
Complement Factor B
Transcription Factor AP-1
Transcriptional Activation
Peptide Hydrolases
Electrophoretic Mobility Shift Assay

ASJC Scopus subject areas

  • Immunology

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Serratia marcescens serralysin induces inflammatory responses through protease-activated receptor 2. / Kida, Yutaka; Inoue, Hiroyoshi; Shimizu, Takashi; Kuwano, Koichi.

In: Infection and Immunity, Vol. 75, No. 1, 01.2007, p. 164-174.

Research output: Contribution to journalArticle

Kida, Yutaka ; Inoue, Hiroyoshi ; Shimizu, Takashi ; Kuwano, Koichi. / Serratia marcescens serralysin induces inflammatory responses through protease-activated receptor 2. In: Infection and Immunity. 2007 ; Vol. 75, No. 1. pp. 164-174.
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