Effect of inhibiting the phosphorylation of signal transducer and activator of transcription-3 on Th2 cell-mediated airway inflammation and airway remodeling in a mouse model of asthma

Abstract

Objective To study the effect of inhibiting the phosphorylation of signal transducer and activator of transcription-3 (STAT3) on Th2 cell-mediated airway inflammation and airway remodeling, and to explore the role of STAT3 in the pathophysiology of bronchial asthma. Methods Forty Balb/c mice were randomly divided into control group(n=10), asthma group(n=10), AG490 by intraperitoneal group (n=10), and AG490 by inhalation group (n=10). The mice were sensitized with ovalbumin to establish the asthmatic model.The histological changes were evaluated by means of HE staining, while total broalchial wall thickness(Wat)and smooth muscle thickness(Wam) were mea-sured by using image analysis system.The percentages of collagen deposition were detected by way of Masson's trichrome staining; the bronchoalveolar lavage fluid (BALF) were collected, the total cell and the cell differentials were counted, the levels of IL-4, IL-5 in BALF were measured by enzyme-linked immunosorbent assay; the lung tissue extracts were analyzed for phosphorylation of STAT3(p-STAT3)by Western blot.The SPSS 13.0 software was used to analyze the data. Results 1.The histological changes by HE staining showed that less inflammatory cells infiltration in airway and around the pulmonary vascular in AG490 administration groups compared with asthmatic group.Wat, Wam and the percentages of collagen deposition in AG490 administration groups was significantly lower than that in asthmatic group(F=49.5, 41.7, 58.2, all P< 0.05).2.The level of p-STAT3 in the lung of AG490 administration groups were significantly lower than those in asthmatic group(F=34.17, P< 0.05).3. The total cells and eosinophils amounts in BALF of AG490 administration groups were significantly lower than those in asthmatic group(F=42.5, 64.7, all P< 0.05). The levels of IL-4, IL-5 in BALF of AG490 administration groups were significantly lower than those in asthmatic group, respectively (F=39.2, 75.1, all P<0.05). Conclusions STAT3 signaling pathway is pivotal in Th2 cell-mediated airway inflammation and airway remodeling in asthmatic models, and AG490 can ameliorate airway inflammation and airway remodeling efficiently by inhibiting the phosphorylation of STAT3, and targeting this signaling pathway may be a novel therapy for asthma. Key words: Asthma; Th2 type cell; Airway inflammation; Airways remodeling; Signal transducer and activator of transcription-3