LTB4 Promotes Acute Lung Injury via Upregulating the PLCε-1/TLR4/NF-κB Pathway in One-Lung Ventilation.
LTB4 Promotes Acute Lung Injury via Upregulating the PLCε-1/TLR4/NF-κB Pathway in One-Lung Ventilation.
复制标题
LTB4 通过上调单肺通气中的 PLC δ-1/TLR4/NF- δ B 通路促进急性肺损伤
DOI：
10.1155/2022/1839341
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Luo J;Ma Q;Tang H;Zou X;Guo X;Hu Y;Zhou K;Liu R
机械通气（MV）可增加肺组织炎症反应，破坏肺组织屏障，引起急性肺损伤（ALI），甚至死亡。然而，MV诱导的ALI中的炎症相关分子和途径在很大程度上仍然未知。因此，本研究的目的是研究一种新的炎症相关分子，白三烯B4（LTB 4），在ALI中的作用和机制。 通过功能丧失实验检测LTB 4在单肺通气（OLV）模型中的功能。HE染色观察肺组织病理变化。在功能上，采用PLCε-1敲低和Toll样受体4（TLR 4）/NF-κB通路抑制剂检测LTB 4对磷脂酶Cε（PLCε-1）/TLR 4/NF-κ B（NF-κB B）通路的调节作用。通过RT-qPCR和蛋白质印迹法测定基因和蛋白质的水平。ELISA法检测炎症细胞因子和趋化因子的水平。 在此，我们发现LTA 4 H、白三烯B（4）受体1（BLT 1）、LTB 4和PLCε-1在OLV大鼠中上调，并且与肺组织的炎症激活和肺通透性改变相关。抑制LTB 4可通过抑制炎性激活和肺组织通透性改变减轻OLV诱导的ALI。LTB 4通过激活PLCε-1/TLR4/NF-κB通路促进OLV诱导的ALI。 LTB 4通过激活PLCε-1/TLR4/NF-κB通路诱导OLV大鼠ALI。我们的研究结果可能为OLV诱导的ALI提供一种新的潜在治疗方法。
Mechanical ventilation (MV) can provoke acute lung injury (ALI) by increasing inflammation activation and disrupting the barrier in lung tissues even causing death. However, the inflammation-related molecules and pathways in MV-induced ALI remain largely unknown. Hence, the purposes of this study are to examine the role and mechanism of a novel inflammation-related molecule, leukotriene B4 (LTB4), in ALI. The functions of LTB4 in one-lung ventilation (OLV) model were detected by the loss-of-function experiments. H&E staining was used to examine the pathologic changes of lung tissues. Functionally, PLCε-1 knockdown and Toll-like receptor 4 (TLR4)/NF-κB pathway inhibitor were used to detect the regulatory effects of LTB4 on the phospholipase Cε (PLCε-1)/TLR4/nuclear factor-kappa B (NF-κB) pathway. The levels of genes and proteins were determined by RT-qPCR and western blotting assay. The levels of inflammation cytokines and chemokines were measured by ELISA. Here, we found LTA4H, leukotriene B (4) receptor 1 (BLT1), LTB4, and PLCε-1 upregulated in OLV rats and associated with inflammatory activation and lung permeability changes of lung tissues. Inhibition of LTB4 alleviated the OLV-induced ALI by inhibiting inflammatory activation and lung permeability changes of lung tissues. For mechanism analyses, LTB4 promoted OLV-induced ALI by activating the PLCε-1/TLR4/NF-κB pathway. LTB4 induced ALI in OLV rats by activating the PLCε-1/TLR4/NF-κB pathway. Our findings might supply a new potential therapeutic for OLV-induced ALI.
登录
查看更多内容
影响因子：
9.8
作者：
Majumdar, Ritankar;Tameh, Aidin Tavakoli;Parent, Carole A.
通讯作者：
Parent, Carole A.
影响因子：
5.6
作者：
Lv, Hui;Li, Jie;Che, Yu-Qin
通讯作者：
Che, Yu-Qin
影响因子：
11.4
作者：
Kelley, GG;Reks, SE;Smrcka, AV
通讯作者：
Smrcka, AV
影响因子：
3.1
作者：
Cao, Chao;Yin, Chengfen;Chai, Yanfen
通讯作者：
Chai, Yanfen
影响因子：
3.6
作者：
Meng, Lu;Li, Longyun;Zhao, Guoqing
通讯作者：
Zhao, Guoqing