Macrophage β-arrestin-1 deteriorates DSS-induced colitis through interaction with NF-κB signaling

文献类型： 外文期刊

第一作者： Ke, Ping

作者： Ke, Ping;Zhu, Dan-Ni;Liu, Meng-Zhen;Yan, Hui;Zhao, Qing-Jie;Liu, Chong;Ke, Ping;Du, Jing;Wei, Wei;Chen, Xiong-Wen;Chen, Xiong-Wen

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关键词： beta-arrestin-1; Ulcerative colitis; Macrophage; NF-kappa B; Inflammation

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：5.6； 五年影响因子：5.6 ）

ISSN： 1567-5769

年卷期： 2024 年 130 卷

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收录情况： SCI

摘要： beta-arrestin-1 has been demonstrated to participate in the regulation of inflammatory reactions in several diseases. Thus, this study aimed to investigate the role of macrophage beta-arrestin-1 in the pathogenesis and progression of ulcerative colitis (UC). A myeloid beta-arrestin-1 conditional knockout mouse model was generated to explore the role of macrophage beta-arrestin-1. DSS was employed for the establishment of an ulcerative colitis mouse model, using TNF-alpha as an inflammatory stressor in vitro. The expression level of beta-arrestin-1 was detected via western blot and immunofluorescence assays, whilst disease severity was evaluated by clinical score and H&E staining in the DSS-induced colitis model. In the in vitro experiments, the levels of inflammatory cytokines were examined using real-time PCR. NF-kappa B activation was detected through the double luciferase reporter system, western blot, and electrophoretic mobility shift assay (EMSA). BAY11-7082 was used to inhibit NF-kappa B activation. Our results exposed that the level of beta-arrestin-1 was increased in monocytes/macrophages derived from DSS-induced colitis mice or under the TNF-alpha challenge. Moreover, conditionally knocking out the expression of myeloid beta-arrestin-1 alleviated disease severity, while knocking out the expression of beta-arrestin-1 decreased the levels of inflammatory cytokines. Additionally, NF-kappa B was identified as a central regulatory element of beta-arrestin-1 promoter, and using BAY11-7082 to inhibit NF-kappa B activation lowered the level of beta-arrestin-1 under TNF-alpha challenge. beta-arrestin1 led to the activation of the NF-kappa B signaling pathway by enhancing binding to I kappa B alpha and IKK under the TNF-alpha challenge. Taken together, our findings demonstrated macrophage beta-arrestin-1 contributes to the deterioration of DSS-induced colitis through the interaction with NF-kappa B signaling, thus highlighting a novel target for the treatment of UC.

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