Cardamine komarovii flower extract reduces lipopolysaccharide-induced acute lung injury by inhibiting MyD88/TRIF signaling pathways
Cardamine komarovii flower extract reduces lipopolysaccharide-induced acute lung injury by inhibiting MyD88/TRIF signaling pathways
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碎米荠花提取物通过抑制 MyD88/TRIF 信号通路减少脂多糖诱导的急性肺损伤
DOI：
10.1016/s1875-5364(19)30053-6
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发表时间：
2019-06-01
影响因子：
4.6
通讯作者：
Jiang Jun
中科院分区：
文献类型：
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作者：
Chen Qi;Zhang Ke-Xin;Jiang Jun
在本研究中，我们观察了豆蔻碱花(CKF)对内毒素(LPS)诱导的急性肺损伤(ALI)的抗炎作用。我们检测了CKF甲醇提取物对内毒素诱导的巨噬细胞(PM)促炎症介质NO和前列腺素E_2(PGE_2)、促炎细胞因子(IL-1β、TNF-α和IL-6)产生及MyD88/TRIF信号通路相关蛋白表达水平的影响。免疫荧光法检测核转录因子-kappaB-p65的核转位。体内实验建立ALI模型，检测小鼠支气管肺泡灌洗液(BALF)中炎性细胞和炎性因子(IL-1β、TNF-α、IL-6)的数量。HE染色评价肺组织病理损伤程度。结果表明，CKF通过抑制炎症介质iNOS和COX-2的合成，减少炎症介质NO和PGE2的产生。此外，CKF还可下调IL-1β、TNF-α和IL-6的mRNA水平，从而抑制炎症因子的产生。机制研究表明，CKF通过调节依赖于MyD88/TRIF的信号通路，具有良好的抗炎作用。免疫细胞化学染色显示，CKF提取物可减弱脂多糖诱导的核因子-kB p65亚基从胞浆向核内的移位。体内实验表明，CKF治疗后小鼠BALF中炎性细胞数量和IL-1β水平下降。肺组织病理组织学观察显示，CKF能明显改善内毒素刺激后大鼠肺泡间质细胞和肺泡细胞的清除和浸润。综上所述，我们的结果提示CKF通过抑制MyD88/TRIF信号通路来抑制内毒素诱导的炎症反应，从而保护小鼠免受内毒素诱导的ALI。
In the present study, we investigated anti-inflammatory effect of Cardamine komarovii flower (CKF) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We determined the effect of CKF methanolic extracts on LPS-induced pro-inflammatory mediators NO and prostaglandin E2 (PGE2), production of pro-inflammatory cytokines (IL-1 beta, TNF-alpha, and IL-6), and related protein expression levels of MyD88/TRIF signaling pathways in peritoneal macrophages (PMs). Nuclear translocation of NF-kappa B-p65 was analyzed by immunofluorescence. For the in vivo experiments, an ALI model was established to detect the number of inflammatory cells and inflammatory factors (IL-1 beta, TNF-alpha, and IL-6) in bronchoalveolar lavage fluid (BALF) of mice. The pathological damage in lung tissues was evaluated through H&E staining. Our results showed that CKF can decrease the production of inflammatory mediators, such as NO and PGE2, by inhibiting their synthesis-related enzymes iNOS and COX-2 in LPS-induced PMs. In addition, CKF can downregulate the mRNA levels of IL-1 beta, TNF-alpha, and IL-6 to inhibit the production of inflammatory factors. Mechanism studies indicated that CKF possesses a fine anti-inflammatory effect by regulating MyD88/TRIF dependent signaling pathways. Immunocytochemistry staining showed that the CKF extract attenuates the LPS-induced translocation of NF-kB p65 subunit in the nucleus from the cytoplasm. In vivo experiments revealed that the number of inflammatory cells and IL-1 beta in BALF of mice decrease after CKF treatment. Histopathological observation of lung tissues showed that CKF can remarkably improve alveolar clearance and infiltration of interstitial and alveolar cells after LPS stimulation. In conclusion, our results suggest that CKF inhibits LPS-induced inflammatory response by inhibiting the MyD88/TRIF signaling pathways, thereby protecting mice from LPS-induced ALI.