Chronic rhinosinusitis with polyps and without polyps is associated with increased expression of suppressors of cytokine signaling 1 and 3

Abstract

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) or without nasal polyps (CRSsNP) is associated with expression of various cytokines. Suppressors of cytokine signaling (SOCS) regulate cytokine activity in a variety of cells, modulating inflammatory responses. Objective: We analyzed the expression and distribution pattern of SOCS1 and SOCS3 in CRSwNP and CRSsNP, and their cytokine-driven expression regulation in sinus mucosa. In addition, the expression levels of various cytokines were evaluated in CRSwNP and CRSsNP. Methods: The expression levels of SOCS1 and SOCS3 in CRSwNP and CRSsNP and in control samples were assessed by using real-time PCR, Western blot, and immunohistochemistry. Nasal epithelial cell culture was used to elucidate the effect of IL-4, IL-5, IL-6, IL-10, IL-13, IFN-gamma, TNF-alpha, and TGF-beta 1 on SOCS1 and SOCS3 expression in sinus mucosa. The expression levels of these cytokines were also evaluated in normal and inflammatory sinus mucosa by using real-time PCR and Western blot. Results: The expression levels of SOCS1 and SOCS3 were increased in CRS, irrespective of the presence of nasal polyp, and they were distributed in superficial epithelium, submucosal glands, and vascular endothelium in sinus mucosa. SOCS1 was induced by IL-4, IL-13, IFN-gamma, and TNF-alpha, while SOCS3 expression was upregulated by IL-6, IL-13, IFN-gamma, and TNF-alpha. IL-4 and IL-13 levels were increased in CRSwNP, while IL-4, IFN-gamma, TNF-alpha, and TGF-beta 1 levels were increased in CRSsNP. Conclusion: SOCS1 and SOCS3 are increased in CRS, irrespective of nasal polyp presence. This may be a response to elevated levels of various cytokines increasingly expressed in inflammatory sinus mucosa. (J Allergy Clin Immunol 2013;131:772-80.)