1. Forsythoside A inhibits adhesion and migration of monocytes to type II alveolar epithelial cells in lipopolysaccharide-induced acute lung injury through upregulating miR-124.
- Author
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Lu ZB, Liu SH, Ou JY, Cao HH, Shi LZ, Liu DY, Tian CY, Zheng YR, Zhou HL, Liu JS, and Yu LZ
- Subjects
- Acute Lung Injury chemically induced, Acute Lung Injury pathology, Animals, Chemokine CCL2 antagonists & inhibitors, Chemokine CCL2 biosynthesis, Dose-Response Relationship, Drug, Glycosides therapeutic use, Lipopolysaccharides, Mice, Mice, Inbred BALB C, MicroRNAs genetics, Pulmonary Alveoli drug effects, Up-Regulation drug effects, Acute Lung Injury prevention & control, Cell Adhesion drug effects, Cell Movement drug effects, Epithelial Cells drug effects, Glycosides pharmacology, MicroRNAs biosynthesis, Monocytes drug effects, Pulmonary Alveoli cytology
- Abstract
Acute lung injury (ALI) is a severe disease for which effective drugs are still lacking at present. Forsythia suspensa is a traditional Chinese medicine commonly used to relieve respiratory symptoms in China, but its functional mechanisms remain unclear. Therefore, forsythoside A (FA), the active constituent of F. suspensa, was studied in the present study. Inflammation models of type II alveolar epithelial MLE-12 cells and BALB/c mice stimulated by lipopolysaccharide (LPS) were established to explore the effects of FA on ALI and the underlying mechanisms. We found that FA inhibited the production of monocyte chemoattractant protein-1 (MCP-1/CCL2) in LPS-stimulated MLE-12 cells in a dose-dependent manner. Moreover, FA decreased the adhesion and migration of monocytes to MLE-12 cells. Furthermore, miR-124 expression was upregulated after FA treatment. The luciferase report assay showed that miR-124 mimic reduced the activity of CCL2 in MLE-12 cells. However, the inhibitory effects of FA on CCL2 expression and monocyte adhesion and migration to MLE-12 cells were counteracted by treatment with a miR-124 inhibitor. Critically, FA ameliorated LPS-induced pathological damage, decreased the serum levels of tumor necrosis factor-α and interleukin-6, and inhibited CCL2 secretion and macrophage infiltration in lungs in ALI mice. Meanwhile, administration of miR-124 inhibitor attenuated the protective effects of FA. The present study suggests that FA attenuates LPS-induced adhesion and migration of monocytes to type II alveolar epithelial cells though upregulating miR-124, thereby inhibiting the expression of CCL2. These findings indicate that the potential application of FA is promising and that miR-124 mimics could also be used in the treatment of ALI., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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