Department of Pathogen Biology, College of Basic Medicine, Hubei University of Chinese Medicine, Wuhan, 430065, China.
College of Acupuncture and Moxibustion, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Inflammation. 2018 Jun;41(3):859-869. doi: 10.1007/s10753-018-0740-8.
In this study, we aimed to investigate the effect of electro-acupuncture (EA) at the Zusanli acupoint (ST36) on interleukin (IL)-33-mediated mast cell activation. Firstly, 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis (ACD) in rats was developed with or without EA treatment. Then, rat peritoneal mast cells (RPMCs) were obtained and cultured in the presence of IL-33. EA treatment relieved ear swelling and reduced mast cell infiltration in the local inflammation area with DNFB challenge, accompanying the decrement of IL-33 production. RPMCs isolated from ACD rats with EA treatment showed significant downregulation of IL-6, TNF-α, IL-13, and MCP-1 production following IL-33 stimulation. However, there was no obvious difference in surface ST2 receptor expression among different groups. In addition, EA selectively altered IL-33 signaling, suppressing p38 phosphorylation as well as NF-κB- and AP-1-mediated transcription but not Akt phosphorylation. Importantly, EA lowered microRNA (miR)-155 expression in the RPMCs, which presented a positive correlation with IL-33-induced IL-6 production. Furthermore, overexpression of miR-155 in the RPMCs was established following miR-155 mimic transfection. RPMCs with the overexpressed miR-155 displayed an obvious increment of inflammatory cytokine and abrogated the inhibitive effect of EA on NF-κB- and AP-1-regulated transcription in response to IL-33 compared with those without transfected-miR-155. These findings demonstrate EA treatment inhibits NF-κB and AP-1 activation as well as promotes the negative feedback regulation of IL-33 signaling via targeting miR-155 in mast cells, which contribute to the anti-inflammatory effect of EA on DNFB-induced ACD in rats.
在这项研究中，我们旨在探讨电针对足三里穴位（ST36）的影响，以介导肥大细胞活化的白细胞介素（IL）-33。首先，用或不用电针（EA）治疗，在大鼠中诱导 2,4-二硝基氟苯（DNFB）诱导的过敏性接触性皮炎（ACD）。然后，获得大鼠腹膜肥大细胞（RPMCs）并在 IL-33 的存在下培养。EA 治疗缓解了耳肿胀，并减少了局部炎症区域中肥大细胞的浸润，同时降低了 IL-33 的产生。EA 治疗的 ACD 大鼠分离的 RPMCs 在受到 IL-33 刺激后，IL-6、TNF-α、IL-13 和 MCP-1 的产生明显下调。然而，不同组之间表面 ST2 受体表达没有明显差异。此外，EA 选择性地改变了 IL-33 信号，抑制了 p38 磷酸化以及 NF-κB 和 AP-1 介导的转录，但不抑制 Akt 磷酸化。重要的是，EA 降低了 RPMCs 中的 microRNA（miR）-155 表达，这与 IL-33 诱导的 IL-6 产生呈正相关。此外，通过 miR-155 模拟物转染建立了 RPMCs 中 miR-155 的过表达。与未转染-miR-155 的 RPMCs 相比，过表达 miR-155 的 RPMCs 显示出明显增加的炎症细胞因子，并消除了 EA 对 IL-33 反应中 NF-κB 和 AP-1 调节转录的抑制作用。这些发现表明，EA 治疗通过靶向肥大细胞中的 miR-155 抑制 NF-κB 和 AP-1 的激活，并促进 IL-33 信号的负反馈调节，从而有助于 EA 对大鼠 DNFB 诱导的 ACD 的抗炎作用。
