高密度脂蛋白在炎症状态下促进II型肺泡上皮细胞的增殖和迁移。

High density lipoprotein promoting proliferation and migration of type II alveolar epithelial cells during inflammation state.

作者信息

Yu Zhongji, Jin Jingru, Wang Yuhui, Sun Jian

机构信息

The Fourth Affiliated Hospital of Nanchang University, Nanchang, 330003, China.

People's Hospital of Shangrao City, Shangrao, 334000, China.

出版信息

Lipids Health Dis. 2017 May 18;16(1):91. doi: 10.1186/s12944-017-0482-x.

BACKGROUND

To investigate the effect and mechanism of high density lipoprotein (HDL) on type II alveolar epithelial cells during inflammation state.

METHODS

The original generation of type II alveolar epithelial cells were separated in rats and treated with PBS/LPS/HDL/HDL + LPS. To observe the proliferation and migration of type II alveolar epithelial cells with bromodeoxyuridine(BrdU) assay, transwell assay and wound healing experiments. In addition, western blot detected the expression of TP-binding cassette transporter A1 (ABCA1), cystic fibrosis transmembrane conductance regulator (CFTR) and the phosphorylation of AKT/extracellular signal-regulated kinase(ERK)/mitogen-activated protein kinase(MAPK). Enzyme-linked immunosorbent assay (ELISA) tested the secretion of tumor necrosis factor a(TNF-a)/interleukin 1a(IL-1a)/IL-6.

RESULTS

HDL promoted the proliferation (↑17%, p < 0.001 HDL+ LPS vs. LPS) and migration (wounding healing: ↑93%, p < 0.001 HDL+ LPS vs. LPS; transwell migration: ↑154%, p < 0.001 HDL+ LPS vs. LPS) of type II alveolar epithelial cells. Furthermore, HDL increased the phosphorylation of MAPK, but not AKT/ERK. And HDL decreased the secretion of TNF-a (↓46%, p < 0.01 HDL+ LPS vs. LPS) and IL-1a (↓45%, p < 0.001 HDL+ LPS vs. LPS), but not IL-6. In addition, HDL up-regulated the expression of ABCAI (↑99%, p < 0.001 HDL vs. CON) and down-regulated the expression of CFTR (↓25%, p < 0.05 HDL vs. CON) in type II alveolar epithelial cells.

CONCLUSIONS

HDL increases the phosphorylation of MAPK, which promotes the proliferation and migration of type II alveolar epithelial cells. And it decreased the secretion of TNF-a/IL-1a and the expression of CFTR. All these suggest that HDL plays an important role in anti-inflammatory effect in inflammation state of lung.

背景

研究高密度脂蛋白（HDL）在炎症状态下对II型肺泡上皮细胞的作用及机制。

方法

分离大鼠原代II型肺泡上皮细胞，并用PBS/LPS/HDL/HDL + LPS处理。采用溴脱氧尿苷（BrdU）检测、Transwell检测和伤口愈合实验观察II型肺泡上皮细胞的增殖和迁移。此外，蛋白质印迹法检测三磷酸结合盒转运体A1（ABCA1）、囊性纤维化跨膜传导调节因子（CFTR）的表达以及AKT/细胞外信号调节激酶（ERK）/丝裂原活化蛋白激酶（MAPK）的磷酸化。酶联免疫吸附测定（ELISA）检测肿瘤坏死因子α（TNF-α）/白细胞介素1α（IL-1α）/IL-6的分泌。

结果

HDL促进II型肺泡上皮细胞的增殖（HDL + LPS组比LPS组↑17%，p < 0.001）和迁移（伤口愈合：HDL + LPS组比LPS组↑93%，p < 0.001；Transwell迁移：HDL + LPS组比LPS组↑154%，p < 0.001）。此外，HDL增加MAPK的磷酸化，但不增加AKT/ERK的磷酸化。HDL减少TNF-α（HDL + LPS组比LPS组↓46%，p < 0.01）和IL-1α（HDL + LPS组比LPS组↓45%，p < 0.001）的分泌，但不减少IL-6的分泌。另外，HDL上调II型肺泡上皮细胞中ABCA1的表达（HDL组比对照组↑99%，p < 0.001），下调CFTR的表达（HDL组比对照组↓25%，p < 0.05）。