Suplatast tosilate ameliorates airway hyperreactivity and inflammation through inhibition of the GATA-3/IL-5 signaling pathway in asthmatic rats

Abstract

Airway hyperreactivity and inflammation are important factors in the aggravation of lung function. Suplatast tosilate (IPD) is a novel and unique anti-asthma clinical compound. However, the mechanisms of IPD action in the inhibition of asthma remain to be elucidated. The present study aimed to investigate the role of the GATA binding protein 3 (GATA-3)/interleukin (IL)-5 signaling pathway in IPD-induced inhibition of asthma. Sprague-Dawley rats were sensitized by intraperitoneal injection with ovalbumin (OVA) to establish an animal model of asthma. IPD was administered continuously (C-IPD) or at a later stage (L-IPD). Budesonide (BUD) was used as a positive control. Airway resistance and the expression of genes at the mRNA and protein levels were measured. Morphological changes in lung tissue and the percentage of eosinophils (EOS) in peripheral blood were observed and correlation analysis was performed. The results revealed that sensitization by OVA significantly increased airway resistance and the percentage of EOS in peripheral blood and induced significant inflammatory changes in lung tissue, as demonstrated by thick epithelium, goblet cell hyperplasia and submucosal cell infiltration. In addition, sensitization by OVA was found to markedly upregulate IL-5 mRNA and protein expression. Airway resistance was found to positively correlate with the expression of IL-5 in the rat lung tissues. Sensitization by OVA was also observed to markedly enhance GATA-3 protein expression and GATA-3 levels were found to positively correlate with airway resistance and IL-5 levels. Similar to the effect of BUD, treatment with C-IPD or L-IPD was found to significantly attenuate OVA-induced increases in airway resistance and the percentage of EOS in peripheral blood. Notably, treatment with C-IPD or L-IPD markedly reduced the OVA-induced expression of IL-5 and GATA-3. In the present study, IPD intervention was demonstrated to ameliorate airway hyperreactivity and inflammation and the mechanisms may involve inhibition of the GATA-3/IL-5 signaling pathway.