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

Abstract

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.

SPIN: sex-specific and pathway-based interpretable neural network for sexual dimorphism analysis

“…Sex-shared genes include PIK3R1 [ 29 ], HLA-G [ 30 , 31 ] and IKBKB [ 32 ]. Male-specific genes include TGFB1 [ 33 , 34 ], MAPK1 [ 35 ] and IL1B [ 36 , 37 ]; on the other hand, female-specific genes include ALDH3A1 [ 38 ] and ITGB4 [ 39 ] (Supplementary Table 6 ). For the pathway analysis with the asthma data, we identified 132 sex-shared, 5 male-enriched and 6 female-enriched pathways.…”

Leaf Extract of Perilla frutescens (L.) Britt Promotes Adipocyte Browning via the p38 MAPK Pathway and PI3K-AKT Pathway

“…It was interesting to note that AKT- and MAPK-related targets (AKT1, AKT2, MAPK14) were shown in cluster 1, indicating that they may play an important role in the PPI network. MAPK14 belongs to the p38 MAPK family, whose function is to initiate signal-transduction cascades that can finally activate transcription factors when cells are simulated by external stimulation, such as stress or proinflammatory cytokines [ 48 ].…”

Gallic Acid Attenuates Sepsis‐Induced Liver Injury through C/EBPβ‐Dependent MAPK Signaling Pathway

“…C16 (5 mg kg −1 body weight per day) was administered to mice by oral gavage starting 1 day before CLP surgery until sacrificed. [42] Biochemical Analysis: The levels of serum and tissue aspartate transaminase (AST) and alanine aminotransferase (ALT) were gauged by commercial kits (C010-2-1 and C009-2-1; Nanjing Jiancheng Bioengineering Institute, China). These were detected at 510 nm using a UV spectrophotometer following the manufacturer's instructions.…”

“…C16 (5 mg kg −1 body weight per day) was administered to mice by oral gavage starting 1 day before CLP surgery until sacrificed. [ 42 ]…”