Triptolide mitigates radiation-induced pneumonitis via inhibition of alveolar macrophages and related inflammatory molecules.
Triptolide mitigates radiation-induced pneumonitis via inhibition of alveolar macrophages and related inflammatory molecules.
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雷公藤甲素通过抑制肺泡巨噬细胞和相关炎症分子减轻辐射诱发的肺炎
DOI：
10.18632/oncotarget.16456
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发表时间：
2017-07-11
期刊：
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
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作者：
Chen C;Yang S;Zhang M;Zhang Z;Zhang SB;Wu B;Hong J;Zhang W;Lin J;Okunieff P;Zhang L
电离辐射所致的肺损伤是胸部肿瘤放射治疗的主要局限性。我们已经证明雷公藤甲素(TPL)可以减轻IR所致的肺炎和肺纤维化。在这项研究中，我们探索了TPL减轻放射毒性效应的潜在机制。结果表明：(1)肺泡巨噬细胞(AM)是照射后肺组织的主要炎症细胞，并维持在较高水平至少17d，TPL可通过抑制巨噬细胞炎性蛋白-2(MIP-2)及其受体CXCR2的产生而减少。(2)在联合培养的照射肺上皮细胞刺激下，AM产生一组炎症分子，如细胞因子(肿瘤坏死因子-α、IL-6、IL-1α、IL-1β)和趋化因子(MIP-2、MCP-1、LIX)。经TPL处理的AM可减少这些IMS的产生。同时，从受照肺组织分离的AM可显著分泌高水平的IMS，TPL可显著降低IMS的分泌水平。(3)TPL抑制肺泡巨噬细胞吞噬功能和ROS产生。我们的结果表明，TPL通过抑制AM的渗透、IM分泌和吞噬作用来减轻辐射引起的肺部炎症。
Ionizing radiation-induced pulmonary injury is a major limitation of radiotherapy for thoracic tumors. We have demonstrated that triptolide (TPL) could alleviate IR-induced pneumonia and pulmonary fibrosis. In this study, we explored the underlying mechanism by which TPL mitigates the effects of radiotoxicity. The results showed that: (1) Alveolar macrophages (AMs) were the primary inflammatory cells infiltrating irradiated lung tissues and were maintained at a high level for at least 17 days, which TPL could reduce by inhibiting of the production of macrophage inflammatory protein-2 (MIP-2) and its receptor CXCR2. (2) Stimulated by the co-cultured irradiated lung epithelium, AMs produced a panel of inflammative molecules (IMs), such as cytokines (TNF-α, IL-6, IL-1α, IL-1β) and chemokines (MIP-2, MCP-1, LIX). TPL-treated AMs could reduce the production of these IMs. Meanwhile, AMs isolated from irradiated lung tissue secreted significantly high levels of IMs, which could be dramatically reduced by TPL. (3) TPL suppressed the phagocytosis of AMs as well as ROS production. Our results indicate that TPL mitigates radiation-induced pulmonary inflammation through the inhibition of the infiltration, IM secretion, and phagocytosis of AMs.