Xueying Li1, Zhaoqing Han1, Feng Wang2, Jianou Qiao3. 1. Department of Respiratory, Shanghai Ninth People's Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200001, China. 2. Department of Thoracic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200001, China. wangsonggyi1997@163.com. 3. Department of Respiratory, Shanghai Ninth People's Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200001, China. QIAOJO1760@sh9hospital.org.cn.
Abstract
BACKGROUND: Epidemiological studies have revealed a link between atopic dermatitis (AD) and asthma. AS1517499, a selective signal transducer and activation of transcription 6 (STAT6) inhibitor, has been shown to effectively block this connection. In this study, we further explored the underlying mechanism by constructing an AD mouse model. METHODS: Female BALB/c mice were randomly divided into four groups (n = 10/group). The AD mouse model was established by 2,4-dinitrochlorobenzene induction with repeated ovalbumin challenge. AS1517499 and corn oil were used as treatment interventions. The features of airway inflammation, remodeling, and hyperactivity were analyzed. RESULTS: Active use of AS1517499 in AD mice effectively reduced Th2-related cytokine levels, alleviated airway eosinophil and lymphocyte infiltration, and regulated GATA3/Foxp3 levels and subepithelial collagen deposition. These changes might be due to specific blockade of the STAT6 signaling pathway. CONCLUSION: AS1517499 could partially block the association between AD and asthma by specifically inhibiting the STAT6 signaling pathway.
BACKGROUND: Epidemiological studies have revealed a link between atopic dermatitis (AD) and asthma. AS1517499, a selective signal transducer and activation of transcription 6 (STAT6) inhibitor, has been shown to effectively block this connection. In this study, we further explored the underlying mechanism by constructing an AD mouse model. METHODS: Female BALB/c mice were randomly divided into four groups (n = 10/group). The AD mouse model was established by 2,4-dinitrochlorobenzene induction with repeated ovalbumin challenge. AS1517499 and corn oil were used as treatment interventions. The features of airway inflammation, remodeling, and hyperactivity were analyzed. RESULTS: Active use of AS1517499 in AD mice effectively reduced Th2-related cytokine levels, alleviated airway eosinophil and lymphocyte infiltration, and regulated GATA3/Foxp3 levels and subepithelial collagen deposition. These changes might be due to specific blockade of the STAT6 signaling pathway. CONCLUSION: AS1517499 could partially block the association between AD and asthma by specifically inhibiting the STAT6 signaling pathway.
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