Kong Rui, Bai Jun, Yao Qing, Xu Xiaoqing
Department of Rheumatology and Allergy, Xuanwu Hospital, Capital Medical University, Beijing, China.
Graduate School of Capital Medical University, Beijing, China.
Immunol Lett. 2025 Dec;276:107047. doi: 10.1016/j.imlet.2025.107047. Epub 2025 May 29.
Allergic asthma is characterized by persistent chronic airway inflammation, leading to mucus hypersecretion and airway hyperresponsiveness. Dual-specificity phosphatase 14 (DUSP14), a member of the DUSP family, is a key regulator in various biological processes. However, the function of DUSP14 in allergic asthma remains to be elucidated. In this study, we aim to explore the function and mechanism of DUSP14 in asthma-related airway inflammation. In an ovalbumin (OVA) asthma mouse model, DUSP14 was found to be significantly diminished. DUSP14 overexpression relieved airway inflammation and attenuated airway mucus production. In vitro, overexpression of DUSP14 attenuated IL-13-induced cellular inflammation and mucus hypersecretion in bronchial epithelial cells (BEAS-2B). Afterwards, we used the co-immunoprecipitation assay to confirm that DUSP14 interacted with TAK1. DUSP14 overexpression restrained the activation of TAK1 and NF-κB signaling pathway in vitro and in vivo. Taken together, our findings clearly showed that DUSP14 could alleviate airway inflammation by inhibiting TAK1 activity and NF-κB signaling pathway, positioning the DUSP14-TAK1-NF-κB regulatory axis as a potential therapeutic target for allergic asthma.
过敏性哮喘的特征是持续性慢性气道炎症，导致黏液分泌过多和气道高反应性。双特异性磷酸酶14（DUSP14）是DUSP家族的成员，是各种生物过程中的关键调节因子。然而，DUSP14在过敏性哮喘中的功能仍有待阐明。在本研究中，我们旨在探讨DUSP14在哮喘相关气道炎症中的功能和机制。在卵清蛋白（OVA）哮喘小鼠模型中，发现DUSP14显著减少。DUSP14过表达减轻了气道炎症并减少了气道黏液分泌。在体外，DUSP14过表达减轻了白细胞介素-13诱导的支气管上皮细胞（BEAS-2B）的细胞炎症和黏液分泌过多。之后，我们使用免疫共沉淀试验证实DUSP14与TAK1相互作用。DUSP14过表达在体外和体内均抑制了TAK1和核因子-κB信号通路的激活。综上所述，我们的研究结果清楚地表明，DUSP14可通过抑制TAK1活性和核因子-κB信号通路来减轻气道炎症，将DUSP14-TAK1-核因子-κB调节轴定位为过敏性哮喘的潜在治疗靶点。
