Open AccessSerratia marcescens Serralysin Induces Inflammatory Responses through Protease-Activated Receptor 2
Author(s) -
Yutaka Kida,
Hirokazu Inoue,
Takashi Shimizu,
Koichi Kuwano
Publication year - 2007
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01239-06
Subject(s) - serratia marcescens , biology , microbiology and biotechnology , protease , serratia , enterobacteriaceae , receptor , bacteria , enzyme , escherichia coli , biochemistry , pseudomonas , gene , genetics
TheSerratia marcescens -derived protease serralysin is consideredto play an important role in the pathogenesis of infection.Protease-activated receptor 2 (PAR-2) is activated by trypsin and alsoseveral other trypsin-like serine proteases, leading to the modulationof inflammatory and immune responses. However, little is known aboutthe activation of PAR-2 by bacterial proteases and its roles inbacterial infection. In this study, we investigated whetherS.marcescens serralysin activates host inflammatory responsesthrough PAR-2. Our results demonstrated that serralysin inducesinterleukin-6 (IL-6) and IL-8 mRNA expression in a human lung squamouscell carcinoma, EBC-l cells. In addition, serralysin activatedactivator protein 1 (AP-1)-, CCAAT/enhancer-binding protein (C/EBP)-,and nuclear factor-κB (NF-κB)-driven promoters in EBC-1cells. An electrophoretic mobility shift assay showed that serralysinactivates the binding of AP-1, C/EBPβ, and NF-κB in thecells. Inactivation of serralysin resulted in the failure oftransactivation of AP-1-, C/EBP-, and NF-κB-driven promoters inthe cells. Furthermore, serralysin activated AP-1-, C/EBP-, andNF-κB-driven promoters via PAR-2 in HeLa cells. PAR-2antagonist peptides decreased serralysin-induced transactivation ofAP-1-, C/EBP-, and NF-κB-driven promoters in EBC-1 cells.Considered together, these results suggest that serralysin requiresPAR-2 to activate the critical transcription factors AP-1,C/EBPβ, and NF-κB for host inflammatoryresponses.