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荷叶碱通过抑制树突状细胞的活化来减轻 HDM 诱导的过敏炎症。

Neferine Attenuates HDM-Induced Allergic Inflammation by Inhibiting the Activation of Dendritic Cell.

机构信息

Inflammation and Allergic Diseases Research Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.

出版信息

Inflammation. 2023 Dec;46(6):2433-2448. doi: 10.1007/s10753-023-01891-6. Epub 2023 Sep 13.

Abstract

House dust mite (HDM) acts as an environmental antigen that might cause chronic allergic diseases. Neferine (NEF) shows anti-inflammation therapeutic effects. This study is to explore the protection role of NEF against HDM-induced allergic inflammation. HDM-induced allergic asthmatic C57BL/6J mice models were established. Differential histological staining was used to analyze lung tissue pathological scores. Flow cytometry was used to analyze subtypes and biomarker expression of immune cells. RT-PCR and ELISA were used to test cytokines-related gene and/or protein expression levels. Western blot was performed to investigate the signaling pathway that mediates allergic inflammation from mice lung tissue and bone marrow-derived dendritic cells (BMDCs). H&E and PAS staining results indicate NEF significantly attenuated inflammatory index and the percentage of goblet cells in the lung tissue induced by HDM. The HDM-elevated TH2 and TH17 cells were significantly decreased by NEF; inflammatory cytokines Il-4, Il-13 and Il-17 were dramatically downregulated in the NEF plus HDM group compared with HDM alone. CD40 and CD86 DCs, eosinophils and mast cells, and ILC2 cells were decreased by NEF which was elevated under HDM stimulation. In vivo and ex vivo investigations indicated NEF can attenuate the activated NF-κB signaling induced by HDM is involved in allergic inflammatory immune response and regulates cytokines-related gene expression. HDM-activated DCs promoted differentiation of TH2 and TH17 cells but were attenuated by NEF. This study suggests NEF interrupts the overexpression of some cytokines released by DCs, TH2, and TH17 cells; NEF attenuates HDM-induced allergic inflammation via inhibiting NF-κB signaling of DCs.

摘要

屋尘螨(HDM)作为一种环境抗原,可能导致慢性过敏性疾病。小檗碱(NEF)具有抗炎治疗作用。本研究旨在探讨 NEF 对 HDM 诱导的过敏性炎症的保护作用。建立 HDM 诱导的过敏性哮喘 C57BL/6J 小鼠模型。采用差异组织学染色分析肺组织病理评分。流式细胞术分析免疫细胞亚群和标志物表达。RT-PCR 和 ELISA 检测细胞因子相关基因和/或蛋白表达水平。Western blot 检测介导过敏炎症的信号通路。H&E 和 PAS 染色结果表明,NEF 可显著减轻 HDM 诱导的肺部炎症指数和杯状细胞百分比。NEF 显著降低了 HDM 上调的 TH2 和 TH17 细胞;与单独 HDM 组相比,NEF 加 HDM 组中炎症细胞因子 Il-4、Il-13 和 Il-17 显著下调。NEF 降低了在 HDM 刺激下升高的 CD40 和 CD86 DCs、嗜酸性粒细胞和肥大细胞以及 ILC2 细胞。体内和体外研究表明,NEF 可以减轻由 HDM 诱导的 NF-κB 信号激活,参与过敏炎症免疫反应,并调节细胞因子相关基因表达。HDM 激活的 DCs 促进 TH2 和 TH17 细胞的分化,但被 NEF 减弱。本研究表明,NEF 阻断了 DCs、TH2 和 TH17 细胞释放的某些细胞因子的过度表达;NEF 通过抑制 DCs 的 NF-κB 信号通路来减轻 HDM 诱导的过敏炎症。

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