TNF- Regulates the Glucocorticoid Receptor Alpha Expression in Human Nasal Epithelial Cells Via p65-NF-b and p38-MAPK Signaling Pathways

Background: Tumor necrosis factor (TNF)-alpha induces changes in the glucocorticoid receptor (GR) isoforms' expression in human nasal epithelial cells (HNECs) in chronic rhinosinusitis (CRS).Objective: However, the underlying mechanism of TNF-alpha induced GR isoforms' expression in HNECs remains unclear. Here, we explored changes in inflammatory cytokines and glucocorticoid receptor alpha isoform (GR alpha) expression in HNECs.Materials and Methods: To explore the expression of TNF-alpha in nasal polyps and nasal mucosa of CRS, fluorescence immunohistochemical analysis was employed. To investigate changes in inflammatory cytokines and GR alpha expression in HNECs, RT-PCR and western blotting were performed following the cells' incubation with TNF-alpha. Cells were pretreated with the nuclear factor-Kappa B gene binding (NF-Kappa B) inhibitor QNZ, the p38 inhibitor SB203580, and dexamethasone for one hour, then a TNF-alpha. Western blotting, RT-PCR, and immunofluorescence had been utilized for the cells' analysis and the ANOVA for the data analysis.Results: The TNF-alpha fluorescence intensity was mainly distributed in nasal epithelial cells of nasal tissues. TNF-alpha prominently inhibited the expression of GR alpha mRNA from 6 to 24 h in HNECs. GR alpha protein was decreased from 12 to 24 h. Treatment with QNZ, SB203580, or dexamethasone inhibited the TNF-alpha and interleukin (IL)-6 mRNA expression and increased the GR alpha levels.Conclusion: TNF-alpha induced changes in the GR isoforms' expression in HNECs, and it was mediated through p65-NF-Kappa B and p38-MAPK signal transduction pathways, which could be considered a promising neutrophilic CRS treatment.