Interaction Between Serum/Glucocorticoid-Regulated Kinase 1 And Interleukin-6 In Chronic Rhinosinusitis

Purpose: Serum/glucocorticoid-regulated kinase 1 (SGK1) has recently emerged as a critical regulator of inflammatory diseases. In this study, we examined SGK1 expression and its possible pathogenic roles in chronic rhinosinusitis (CRS).Methods: Immunohistochemistry, western blotting, Bio-Plex assay, enzyme-linked immunosorbent assays, and quantitative real-time polymerase chain reaction were performed to assess protein and gene expression levels. The mRNA expression levels of SGK1 and interleukin-6 (IL-6) were extracted from a CRS database to perform correlation analysis. Stable cell lines with SGK1 overexpression (16HBE) and knockdown (A549) were constructed to investigate the interaction between SGK1 and IL-6 in vitro.Results: SGK1 exhibited strong cytoplasmic and nuclear staining in the epithelial layers and the lamina propria of nasal polyps (NPs) and in the mucosal tissues of CRS without nasal polyps (CRSsNP). The mRNA and protein expression levels of SGK1 and IL-6 were significantly increased in NPs and CRSsNP tissues, compared to control tissues. SGK1 phosphorylation was significantly greater in NPs than in CRSsNP tissues (P < 0.01). The mRNA levels of SGK1 and IL-6 were significantly correlated (P < 0.001, r = 0.649). Exposure to IL-6 significantly increased SGK1 expression in cultured dispersed NP cells, 16HBE cells, and A549 cells. IL-6 expression was significantly down-regulated in SGK1-overexpressing 16HBE cells (P < 0.01) and significantly up-regulated in SGK1-knockdown A549 cells (P < 0.05). Administration of GSK650394, a SGK1 inhibitor, significantly increased IL-6 self-induced mRNA expression in cultured dispersed NP cells and 16HBE cells.Conclusions: The interaction between SGK1 and IL-6 may play an anti-inflammatory role in IL-6-induced inflammation in the pathogenesis of CRS.