Resveratrol upregalates PTEN and inhibits MUC5AC expression in ovalbumin (OVA)-induced asthma model mice

Objective: To investigate the anti-asthmatic mechanisms of resveratrol. Methods: An ovalbumin (OVA)-challenged murine model of asthma was used for reseveratrol treatment. PTEN and MUC5AC mRNA and protein expression was assessed by real time PCR and immunochemistry. The lung epithelial cell line 16HBE was used to study the regulation of PTEN and MUC5ACexpression levels by resveratrol in vitro. Results: Resveratrol significantly inhibited OVA-induced airway inflammation, airway remodeling and mucus production. The expression of PTEN was restored following treatment with resveratrol. Correlation efficient analysis showed PTEN expression was associated with the degree of airway remodeling. The inhibition of SIRT1 activity by a SIRT1 inhibitor and RNA interference decreased PTEN protein expression in vitro; however, resveratrol attenuated the decreases in PTEN expression induced by the SIRT1 inhibitor. The mRNA and protein expression levels of MUC5AC were increased in the OVA-challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium-activated chloride channel (mCLCA)3 were also reduced following resveratrol treatment. Resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose-dependent manner in vitro. Conclusion: These data were suggestive of the anti-asthmatic effects of resveratrol in an OVA-induced murine asthma model, which resulted in the up-regulation of PTEN via SIRT1 activation. and in preventing mucus overproduction and MUC5AC expression in vivo.