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

  • Allergy Asthma Clin Immunol. 2022 Feb 17;18(1):12. doi: 10.1186/s13223-022-00652-8.
Xueying Li   #  1 Zhaoqing Han   #  1 Feng Wang  2 Jianou Qiao  3
Affiliations
  • 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. [email protected].
  • 3. Department of Respiratory, Shanghai Ninth People's Hospital Affiliated Shanghai JiaoTong University School of Medicine, No.639, Zhizaoju Road, Shanghai, 200001, China. [email protected].
  • # Contributed equally.
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.

Keywords
AS1517499; Asthma; Atopic dermatitis; STAT6; Th2 cells; Treg cells.
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