The Proinflammatory Effects Of Staphylococcal Aureus Enterotoxin B On Human Nasal Epithelial Cells

Background Currently, the aetiology and pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) are starting to become unraveled. The latest 2003 task force on CRS proposed that CRS is related to a number of different systemic and local host or environmental fators. The interaction between nasal microenvironment and the inflammatory mechanisms of CRS is poorly understood. Bachert and Bernstein provided indirected evidence for the role of staphylococcus aureus in the pathogenesis of CRSwNP. Fisrtly, the presence of specific IgE to staphylococcal enterotoxins (SEs) A and B suggested a possible role of SE in CRS/NP. Secondly, toxin-producing S. arueus was detected in the nasal mucus adjacent to the polyps of approximately 60% CRS/NP patients and three different enterotoxins were isolated including SEA, SEB and toxic shock syndrome toxin-1 (TSST-1). Interestingly, the variableβspecificity for these superantigens was also identified in the polyp lymphocytes. On the basis of the above results, Bernstein proposed the"superantigen hypothesis"to summarize possible inflammatory mechanisms caused by S. arueus and SEs in CRSwNP. The hypothesis emphasizes the importance of nasal microenvironmental factors in the development of CRSwNP. Recent studies have demonstrated that SE can influence the activity of immunomodulatory and pro-inflammatory effector cell types (including epithelial cells), and therefore may have a potentially important role in the pathogenesis of chronic inflammatory disease. Compared with studies on lymphocyte (T and B cells) and other pro-inflammatory cell types (including eosinophils, macrophages, and mast cells, which are known to play key roles in the pathogenesis of inflammatory airway disease), there are comparatively fewer reports investigating the effects of SE on epithelial cells possibly as a proinflammatory cell type.We sought to determine the effects of SEB on the proinflammatory cytokine/chemokine releases of primary cultured human nasal epithelial cells (HNEC), and to compared the response of HNEC from patients with and without CRSwNP.Methods Nasal mucosae were obtained from 40 patients with nasal polyps undergoing polypectomy and 15 patients with obstructive sleep apnea syndrome subjected to partial inferior turbinectomy, Which had not been treated with corticosteroids. After the isolation of HNEC, epithelial cells of nasal polyps (NP) and inferior turbinate (IT) were cultured without serum under stimulus of SEB 1.0, 10, 100ng/ml, IL-Iβ20ng/ml and SEB 10ng/ml+dexamethasone 13ng/ml for 12h,24h and 48h, respectively. The expression of IL-5 and GM-CSF mRNA derived from epithelial cells was detected by in situ hybridization and western blot.Results①The expression of IL-5 and GM-CSF mRNA and protein was time and dose-dependent, and reach to a peak under SEB 10ng/ml for 24h (P<0.05). The expression of IL-5 and GM-CSF mRNA and protein is stronger in epithelial cells from NP than IT (P<0.05).②The expression of IL-5 and GM-CSF mRNA and protein induced by IL-1βis more poor than that by SEB10ng/ml (P<0.05).③T he expression of IL-5 and GM-CSF mRNA and protein is decreased under the stimulus of SEB 10ng/ml+dexamethasone 13 ng/m when compared with the stimulus of SEB 10ng/ml (P<0.05).Conclusion SEB showed proinflammatory effects on HNEC. It is the first time to demonstrate that SEB may induce the expression of IL-5 and GM-CSF in human nasal epithelial cells and cortisteroids may inhibit that.