The involvement of IL-1β/p38MAPK/NF-κB signal transduction pathway in regulating the expression of glucocorticoid receptor isoformsin human nasal epithelia in vitro / 实用医学杂志

ABSTRACT

Objective To explore the possible upstream signal transduction mechanisms responsible for the decrease of glucocorticoid receptor (GR)α/GRβ in chronic rhinosinusitis (CRS) in vitro. Methods The GRα/GRβ decrease cell model was established by IL-1β-induced human nasal epithelia (HNE) in vitro. Changes in the protein and mRNA expression of GRα, GRβ and the key enzymes in the p38MAPK and NF-κB pathways were measured respectively, before and after being induced with different doses of IL-1β and specific inhibitors of p38MAPK and NF-κB. Analysis of variance (ANOVA) was used to analyze the data. Results With IL-1β-induction, the GRα/GRβ ratio declined in both a time-dependent manner and a concentration-dependent manner in HNE, which demonstrated the successful establishment of a GRα/GRβ decrease model in vitro. After cultured HNE were induced with the same set of IL-1β, the p38MAPK and NF-κB signal pathways were also activated. Either a specific inhibitor (SB203580) of the p38MAPK pathway or a specific inhibitor (PDTC) of the NF-κB pathway increased the GRα/GRβ ratio at the meantime of inhibiting their pathways. The expressions of phospho-NF-κBp50 and phospho-NF-κBp65 were significantly decreased by SB203580. PDTC had no influence on the expression of the key enzymes in the p38MAPK. Conclusion The decrease of GRα/GRβ ratio in HNE induced by IL-1β in vitro is induced through the p38MAPK/NF-κB signal pathways.