Interleukin-1β regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways

Background: To explore the upstream signal transduction mechanisms responsible for the imbalanced expression of glucocorticoid receptor (GR) isoforms in chronic rhinosinusitis (CRS) mucosa. Methods: An in vitro model of Glucocorticoid resistance was established by inducing nasal polyp tissue with IL-1 beta. Changes in the protein and mRNA expression of GR alpha, GR beta and the key enzymes in the p38 MAPK and JNK signal pathways were measured, respectively, before and after being induced with different doses of IL-1 beta and specific inhibitors of p38 MAPK, JNK, ERK, PI3K and PKC. The Glucocorticoid sensitivity was measured using in vitro Glucocorticoid binding assay. Analysis of variance (ANOVA) was used to analyze the data. Results: The mRNA and protein expression levels of GR alpha, GR beta and key enzymes of the p38 MAPK and JNK pathways increased both in time-and concentration-dependent manners in IL-1 beta-induced nasal polyp tissue. The expression of GR beta increased more significantly than that of GR alpha, and the GR alpha/GR beta ratio decreased in time-and concentration-dependent manners. Statistically significant differences were found in the GR alpha/GR beta ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1 beta-induced groups and the control groups (P < 0.05). Either a specific inhibitor of the p38 MAPK pathway or a specific inhibitor of the JNK pathway increased the GR alpha/GR beta ratio and the Glucocorticoid affinity. None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms. Conclusion: Our results demonstrated that the imbalanced expression of GR isoforms in nasal polyp tissue induced by IL-1 beta in vitro is mediated through the p38 MAPK and JNK signal pathways.