Chlorogenic acid enhances alveolar macrophages phagocytosis in acute respiratory distress syndrome by activating G protein-coupled receptor 37 (GPR 37)

Background: Impaired alveolar macrophages phagocytosis can contribute to pathogenesis of acute respiratory distress syndrome (ARDS) and negatively impacts clinical outcomes. Chlorogenic acid (CGA) is a naturally occurring polyphenolic compound with potential anti-inflammatory and antioxidant bioactivities. Studies have shown that CGA plays a protective role in ARDS, however, the precise protective mechanism of CGA against ARDS, is still unclear. Purpose: The aim of this study was to investigate whether CGA enhances alveolar macrophages phagocytosis to attenuate lung injury during ARDS. Methods: RAW264.7 cells were stimulated with lipopolysaccharides (100 mu g/ml for 24 h) and treated with CGA (100, 200, and 400 mu M CGA for 1 h) to measure pro-inflammatory cytokine levels, GPR37 expression and macrophages phagocytosis. Mouse models of ARDS induced by cecal ligation and perforation (CLP) surgery were treated with CGA (100 or 200 mg/kg) to investigate lung inflammatory injury and alveolar macrophages phagocytosis. Computational modeling was performed to examine potential binding sites of G protein-coupled receptor 37 (GPR37) with CGA, and the results were validated by interfering with the binding sites. Result: In vitro, CGA notably ameliorated inflammatory response and increased phagocytosis in lipopolysaccharides-induced RAW264.7 cells. In vivo, CGA administration significantly alleviated lung inflammatory injury, decreased the bacteria load in the lung, promoted alveolar macrophages phagocytosis and improved the survival rate in mice with CLP-induced ARDS. Moreover, CGA markedly upregulated the expression of GPR37 in vivo and in vitro. However, the protective effect of CGA against ARDS were reversed after silencing the expression of GPR37. Conclusion: CGA has a protective effect against ARDS and may enhance alveolar macrophages phagocytosis and attenuate lung inflammatory injury by upregulating GPR37 expression.

Automated summary

This study found that CGA enhances alveolar macrophages phagocytosis by upregulating GPR37 expression, thus attenuating lung inflammatory injury.