title: Interleukin-1β regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways.
abstract: 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-1β. Changes in the protein and mRNA expression of GRα, GRβ 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-1β 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 GRα, GRβ and key enzymes of the p38 MAPK and JNK pathways increased both in time- and concentration-dependent manners in IL-1β-induced nasal polyp tissue. The expression of GRβ increased more significantly than that of GRα, and the GRα/GRβ ratio decreased in time- and concentration-dependent manners. Statistically significant differences were found in the GRα/GRβ ratio and the mRNA expression of phospho-p38 MAPK and phospho-JNK between the IL-1β-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 GRα/GRβ ratio and the Glucocorticoid affinity. None of the specific inhibitors of ERK, PI3K or PKC had any influence on the expression of GR isoforms.
  
  
  CONCLUSIONS
  Our results demonstrated that the imbalanced expression of GR isoforms in nasal polyp tissue induced by IL-1β in vitro is mediated through the p38 MAPK and JNK signal pathways.
authors: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.
authors: Zhenlin
authors: Z
authors: Wang
authors: Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Street, Tianhe District, Guangzhou, 510630 PR China.
authors: Peng
authors: P
authors: Li
authors: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.
authors: Qiuhang
authors: Q
authors: Zhang
authors: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.
authors: Haili
authors: H
authors: Lv
authors: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.
authors: Junqi
authors: J
authors: Liu
authors: Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing, 100053 PR China.
authors: Jinyuan
authors: J
authors: Si
keywords: Chronic rhinosinusitis (CRS); Mitogen-activated protein kinase (MAPK); Nasal polyp (NP); Signal transduction
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