Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14

Background: Dysfunction of airway epithelial cells in patients with asthma is closely with the occurrence and development of allergic asthma. Finding the differences of airway epithelium between asthmatic patients and normal patients is helpful to find out new treatment strategies.

Methods: First, three original microarray datasets (GSE89809, GSE41861, GSE104468) from the Gene Expression Omnibus (GEO) dataset were used to assess differentially expressed genes in the epithelial tissues between patients with allergic asthma and healthy controls. Then, 10 ng/mL TGF-β1 treated BEAS-2B cells and rats with ovalbumin induced allergic asthma were performed to confirm our assumption from the gene expression analysis with microarrays.

Results: Top ten hub significant difference genes were obtained by Cytohubba plug-in from GSE41861, and found that Androgen Receptor (AR) was closely associated with the mitogen-activated protein kinase (MAPK) pathway, especially MAPK1 and MAPK14. After treated with the TGF-β1 treated BEAS-2B cells and rats with allergic asthma, we found that 5α-dihydrotestosterone (5α-DHT), AR agonist, significantly decreased the Th2 inflammation (IL-25 and IL-33), MAPK1 and MAPK14 proteins expression in vitro and in vivo. The roles of 5α-DHT were similar with the results of chicanine (a p38 MAPK and ERK1/2 inhibitor), but the roles of 5α-DHT were masked by the C16-PAF (a MAPK and MEK/ERK Activator) treatment.

Conclusion: Androgen Receptor limits the secretion of Th2 inflammatory factors by downregulating MAPK1 and MAPK14 in the TGF-β1 treated BEAS-2B cells and rats with ovalbumin induced allergic asthma, which plays a critical role for the therapeutics of patients with asthma.