Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation
Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation
复制标题
木香内酯通过抑制巨噬细胞活化减轻 HKSA 诱导的急性肺损伤
DOI：
10.1038/s41401-018-0192-6
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发表时间：
2019-08-01
影响因子：
8.2
通讯作者：
Qian, Feng
中科院分区：
文献类型：
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作者：
Chen, Yun-tian;Du, Yao;Qian, Feng
金黄色葡萄球菌(S.金黄色葡萄球菌）感染导致严重的炎症反应并引起急性肺损伤（ALI），最终威胁人类生命。因此，寻找一种能够抑制炎症和减轻ALI的药物具有重要意义。在这里，我们发现木香烃内酯，一种倍半萜内酯，显示出抗炎作用和改善热死。金黄色葡萄球菌（HKSA）诱导的肺炎。木香烃内酯治疗可减轻HKSA诱导的小鼠ALI，其中肺中性粒细胞浸润受到抑制，肺水肿减轻，促炎性细胞因子的产生显著减少。此外，木香烃内酯剂量依赖性地抑制HKSA诱导的巨噬细胞中IL-6、TNF-α、IL-1β和角质形成细胞源性细胞因子（KC）的产生，以及iNOS的表达。此外，木香烃内酯还减弱了p38 MAPK和cAMP反应元件结合蛋白（CREB）的磷酸化。总之，我们的研究结果表明，木香烃内酯是一个有前途的药物，通过抑制MAPK信号通路，减轻细菌诱导的ALI。
Staphylococcus aureus(S. aureus) infection leads to a severe inflammatory response and causes acute lung injury (ALI), eventually threatening human life. Therefore, it is of importance to find an agent to inhibit inflammation and reduce ALI. Here, we found that costunolide, a sesquiterpene lactone, displays anti-inflammatory effects and ameliorates heat-killedS. aureus(HKSA)-induced pneumonia. Costunolide treatment attenuated HKSA-induced murine ALI in which pulmonary neutrophil infiltration was inhibited, lung edema was decreased, and the production of pro-inflammatory cytokines was significantly reduced. In addition, costunolide dose-dependently inhibited the generation of IL-6, TNF-α, IL-1β, and keratinocyte-derived cytokine (KC), as well as the expression of iNOS, in HKSA-induced macrophages. Furthermore, costunolide attenuated the phosphorylation of p38 MAPK and cAMP response element-binding protein (CREB). Collectively, our findings suggested that costunolide is a promising agent for alleviating bacterial-induced ALI via the inhibition of the MAPK signaling pathways.