title: Immunomodulation of nasal epithelial cells by Staphylococcus aureus-derived serine proteases.
abstract: The impact of Staphylococcus aureus in the pathogenesis of chronic rhinosinusitis is not well understood. Therefore, we investigated primary human nasal epithelial cell cultures for their ability to produce IL-8, growth-related oncogene-alpha, and IL-6 via stimulation with trypsin and culture supernatants of different S. aureus strains and phenotypes. Inhibition of cytokine synthesis was performed using a glucocorticoid, a serine protease inhibitor, and a cysteine protease inhibitor. Finally, signal transduction pathways were analyzed by quantifying phosphorylated forms of MAPKs (PI3K, ERK, and p38) and DNA-binding assays that quantified NF-kappaB and its inhibition using BAY11-7085. In vitro studies showed that the induction of IL-8, growth-related oncogene-alpha, and IL-6 by S. aureus culture supernatants was significantly inhibited by the serine protease inhibitor. In contrast, steroids and the cysteine protease inhibitor had little effect. Activation of NF-kappaB was observed after cell treatment with trypsin and bacterial supernatants, and was inhibited by BAY11-7085 and the serine protease inhibitor. S. aureus serine proteases were identified to modulate chemokine synthesis and activate NF-kappaB in nasal epithelial cells, and may therefore be relevant for the pathophysiology of chronic rhinosinusitis.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Münster, Münster, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Rudack
authors.forename: Florian
authors.initials: F
authors.lastname: Sachse
authors.forename: Nils
authors.initials: N
authors.lastname: Albert
authors.forename: Karsten
authors.initials: K
authors.lastname: Becker
authors.forename: Christof
authors.initials: C
authors.lastname: von Eiff
mesh_terms: D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000096:biosynthesis / Q000276:immunology; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology; D006801:Humans; D056747:Immunomodulation / Q000502:physiology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D008666:Metalloendopeptidases / Q000276:immunology*; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000276:immunology*; D012220:Rhinitis / Q000276:immunology*; D057057:Serine Proteases / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology
chemical_list: D054360:Chemokine CXCL1; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D057057:Serine Proteases; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus