The STAT6 inhibitor AS1517499 reduces the risk of asthma in mice with 2,4-dinitrochlorobenzene-induced atopic dermatitis by blocking the STAT6 signaling pathway

STAT6 抑制剂 AS1517499 通过阻断 STAT6 信号通路,降低 2,4-二硝基氯苯诱发的特应性皮炎小鼠哮喘的风险

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作者:Xueying Li #, Zhaoqing Han #, Feng Wang, Jianou Qiao

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.

Conclusion

AS1517499 could partially block the association between AD and asthma by specifically inhibiting the STAT6 signaling pathway.

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.

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