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

Journal of Inflammation

Jinyuan Si²  Junqi Liu²  Haili Lv²  Qiuhang Zhang²  Peng Li¹  Zhenlin Wang² 

[1] 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;Department of Otolaryngology-Head and Neck Surgery, Xuan Wu Hospital, Capital Medical University, 45 Changchun Street, Xicheng District, Beijing 100053, PR China

关键词: Mitogen-activated protein kinase (MAPK);    Signal transduction;    Nasal polyp (NP);    Chronic rhinosinusitis (CRS);   

Others  :  1137208
DOI  :  10.1186/s12950-014-0046-z

 received in 2014-08-21, accepted in 2014-12-18,  发布年份 2015

【 摘 要 】

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.

Conclusion

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.

【 授权许可】

   
2015 Wang et al.; licensee BioMed Central.

【 图 表 】

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