Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated by cAMP-Epac Pathway
Quercetin (Que) as an abundant flavonol element possesses potent antioxidative properties and has protective effect in lipopolysaccharide (LPS)-induced acute lung injury (ALI), but the specific mechanism is still unclear, so we investigated the effect of Que from in vivo and in vitro studies and the related mechanism of cAMP-PKA/Epac pathway. The results in mice suggested that Que can inhibit the release of inflammatory cytokine, block neutrophil recruitment, and decrease the albumin leakage in dose-dependent manners. At the same time, Que can increase the cAMP content of lung tissue, and Epac content, except PKA. The results in epithelial cell (MLE-12) suggested that Que also can inhibit the inflammatory mediators keratinocyte-derived chemokines release after LPS stimulation; Epac inhibitor ESI-09 functionally antagonizes the inhibitory effect of Que; meanwhile, PKA inhibitor H89 functionally enhances the inhibitory effect of Que. Overexpression of Epac1 in MLE-12 suggested that Epac1 enhance the effect of Que. All those results suggested that the protective effect of quercetin in ALI is involved in cAMP-Epac pathway.
Key WordsQuercetin LPS acute lung injury cAMP Epac PKA
THF designed the study and wrote the manuscript. WXF and SSD prepared the LPS-induced lung injury model, harvested the lung samples, and completed the determination of WB, MPO, albumin, and cytokine. LYJ prepared the cell experiment and completed the determination of cytokine. HZQ prepared the plasmids of Epac1 and cultured the MHS cell. ZZW did the histology; YCG and LZG provided support of design and discussion. All authors approved the final version of the paper.
These researches were supported by the National Natural Science Foundation of China (81202980, 30800497, 81100051, 31400751 and 81570056).
Compliance with Ethical Standards
Experimental protocols were approved by the Animal Care Committee of Zhejiang University in accordance with the international guidelines.
Conflict of Interest
The authors declare that they have no conflicts of interest.
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