寇托内酯通过抑制巨噬细胞活化缓解 HKSA 诱导的急性肺损伤。
Costunolide alleviates HKSA-induced acute lung injury via inhibition of macrophage activation.
机构信息
Department of Respiratory Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Department of Infectious Diseases, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, 200240, China.
出版信息
Acta Pharmacol Sin. 2019 Aug;40(8):1040-1048. doi: 10.1038/s41401-018-0192-6. Epub 2019 Jan 15.
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-killed S. 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.
金黄色葡萄球菌（S. aureus）感染会导致严重的炎症反应，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 的药物非常重要。在这里，我们发现，一种倍半萜内酯，木香烃内酯，具有抗炎作用，并能改善热灭活金黄色葡萄球菌（HKSA）诱导的肺炎。木香烃内酯治疗可减轻 HKSA 诱导的小鼠 ALI，抑制肺部中性粒细胞浸润，减少肺水肿，显著降低促炎细胞因子的产生。此外，木香烃内酯还能剂量依赖性地抑制 HKSA 诱导的巨噬细胞中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和角蛋白细胞源性细胞因子（KC）的生成，以及诱导型一氧化氮合酶（iNOS）的表达。此外，木香烃内酯还能减轻 p38 MAPK 和 cAMP 反应元件结合蛋白（CREB）的磷酸化。综上所述，我们的研究结果表明，木香烃内酯是一种有前途的药物，可通过抑制 MAPK 信号通路缓解细菌诱导的 ALI。
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