Effects of grape seed proanthocyanidin extract on airway inflammation and Treg/Th17 balance in asthmatic mice

Abstract

Objective To explore effect of grape seed proanthocyanidin extract(GSPE)on airway inflammation and hyperresponsiveness of ovalbumin-induced murine asthma model and the associated regulatory effect on Treg/Th17 imbalance. Methods A total of 40 mice were randomly assigned to four experimental groups: control, asthma model, low dose GSPE(40 mg/kg), and high dose GSPE(80 mg/kg). Acute asthma model was established with OVA; airway responsiveness of mice in each group was measured with a noninvasive pulmonary function instrument; lung inflammation changes were observed by pathological HE staining; Treg/Th17 cytokines levels in bronchoalveolar lavage fluid were evaluated by ELISA; the expressions of forkhead/winged helix transcription factor(Foxp3)mRNA and retinoid-related orphan receptor gammat(RORγt)mRNA in lung tissue of each group were gained by Real-time PCR method. Results GSPE inhibited ovalbumin-induced increases in airway responsiveness(P<0.05). Histological studies demonstrated that GSPE substantially inhibited OVA-induced airway inflammation in lung tissue.GSPE decreased IL-17A levels and increased IL-10 levels in bronchoalveolar lavage fluid(P<0.05). In the asthma model group, RORγt mRNA expression in lung tissue was significantly higher than that in the control group(P<0.05)and Foxp3 mRNA expression was significantly lower than that in the control group(P<0.05). In the GSPE group, RORγt mRNA expression was lower than that in asthma model group(P<0.05), however the Foxp3 mRNA expression was higher than that in asthma model group(P<0.05). Conclusion GSPE could alleviate airway hyperresponsiveness and airway inflammation of in asthmatic mice.It can modify the asthmatic mice Treg/Th17 imbalance by decreasing IL-17A and increasing IL-10 concentration at the level of cytokines; and also by increasing Foxp3 mRNA expression and inhibiting the expression of RORγt mRNA at the transcriptional level, which provide a new way for treatment of bronchial asthma. Key words: Grape seed proanthocyanidin extract; Asthma; Forkhead/winged helix transcription factor; Retinoid-related orphan receptor gammat