Serratia marcescensSerralysin Induces Inflammatory Responses through Protease-Activated Receptor 2

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-l cells. In addition, serralysin activated activator protein 1 (AP-1)

Protective Role for Protease-Activated Receptor-2 against Influenza Virus Pathogenesis via an IFN-γ-Dependent Pathway

“…Although the effects of PAR 2 in an innate immune response to bacterial infection have been well documented (13,39,40), this study is the first to show a protective role for PAR 2 in the context of viral infection in vivo. However, the overall role of PAR 2 in airway immune responses is not well characterized.…”

“…A role for one member of this family, PAR 2 , in lung inflammatory processes has been investigated in several studies (12,13). On one hand, PAR 2 activation by selective agonists in the lung induces signs of inflammation (recruitment of inflammatory cells and cytokine and chemokine release) (13)(14)(15)(16)(17), and endogenous activation of PAR 2 promotes allergic sensitization and the recruitment of inflammatory cells to the airways (17). On the other hand, PAR 2 agonists inhibit LPS-induced granulocyte recruitment, and PAR 2 -deficient mice displayed more severe lung inflammation in a model of bacterial (Pseudomonas aeruginosa) infection (18).…”

Analysis of Proteinase-activated Receptor 2 and TLR4 Signal Transduction

“…In mice, PAR 2 activation plays a pivotal role in the pathogenesis of periodontitis caused by Porphyromonas gingivalis (15) and in the development of infectious colitis induced by Citrobacter rodentium (16). Exposure of PAR 2 to proteases derived from P. gingivalis (17) or Serratia marcescens (18) induces expression of the antimicrobial peptide ␤-defensin 2 (17), pro-inflammatory cytokines and chemokines, e.g. interleukin (IL)-6 and IL-8 (18), as well as activation of the transcription factors AP-1, C/EBP␤, and NF-B (18) in human gingival cells (17) and lung epithelial cells (18).…”

“…Exposure of PAR 2 to proteases derived from P. gingivalis (17) or Serratia marcescens (18) induces expression of the antimicrobial peptide ␤-defensin 2 (17), pro-inflammatory cytokines and chemokines, e.g. interleukin (IL)-6 and IL-8 (18), as well as activation of the transcription factors AP-1, C/EBP␤, and NF-B (18) in human gingival cells (17) and lung epithelial cells (18). The house dust mite allergens, Der p3 and Der p9 serine proteases, also induce proinflammatory responses in human airway epithelial cells via PAR 2 activation (19,20).…”

Resistance of Bacteria to the Factors of the Innate Immune System, Mediated by Bacterial Proteases

“…Metalloprotease LasB (family M04.005) of Pseudomonas aeruginosa can destroy the extracellular domains of PAR-2 receptor and inactivate it [49]. The serralysin (family M10.051) of Serratia marcescens was able to activate PAR-2 receptor in carcinoma of the airways and HeLa cells lines, with subsequent activation of pro-inflammatory signaling pathways experimental cells [50]. The same ability to activate this type of receptor on epithelial cells of the stomach is set to proteases from Helicobacter pylori, which resulted in the increased production of proinflammatory IL-8 in the centers of colonization of this bacterium.…”