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Infection and Immunity, January 2007, p. 164-174, Vol. 75, No. 1
0019-9567/07/$08.00+0     doi:10.1128/IAI.01239-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Serratia marcescens Serralysin Induces Inflammatory Responses through Protease-Activated Receptor 2

Department of Bacteriology,¹ Radioisotope Institute for Basic and Clinical Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka 830-0011, Japan²

Received 4 August 2006/ Returned for modification 14 September 2006/ Accepted 2 October 2006

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-l cells. In addition, serralysin activated activator protein 1 (AP-1)-, CCAAT/enhancer-binding protein (C/EBP)-, and nuclear factor-B (NF-B)-driven promoters in EBC-1 cells. An electrophoretic mobility shift assay showed that serralysin activates the binding of AP-1, C/EBPß, and NF-B in the cells. Inactivation of serralysin resulted in the failure of transactivation of AP-1-, C/EBP-, and NF-B-driven promoters in the cells. Furthermore, serralysin activated AP-1-, C/EBP-, and NF-B-driven promoters via PAR-2 in HeLa cells. PAR-2 antagonist peptides decreased serralysin-induced transactivation of AP-1-, C/EBP-, and NF-B-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/EBPß, and NF-B for host inflammatory responses.

Published ahead of print on 16 October 2006.

Editor: W. A. Petri, Jr.

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