Coelonin protects against PM2.5-induced macrophage damage via suppressing TLR4/NF-κB/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro

One of the important monitoring indicators of the air pollution is atmospheric fine particulate matter (PM2.5), which can induce lung inflammation after inhalation. Coelonin can alleviate PM2.5-induced macrophage damage through anti-inflammation. However, its molecular mechanism remains unclear. We hypothesized that macrophage damage may involve the release of inflammatory cytokines, activation of inflammatory pathways, and pyrosis induced by inflammasome. In this study, we evaluated the anti-inflammation activity of coelonin in PM2.5-induced macrophage and its mechanism of action. Nitric oxide (NO) and reactive oxygen species (ROS) production were measured by NO Assay kit and dichlorofluorescein-diacetate (DCFH-DA), and apoptosis were measured by Flow cytometry and TUNEL staining. The concentration of inflammatory cytokines production was measured with cytometric bead arrays and ELISA kits. The activation of NF-kappa B signaling pathway and NLRP3 inflammasome were measured by immunofluorescence, quantitative reverse transcription-polymerase chain reaction and western blot. As expected, coelonin pretreatment reduced NO production significantly as well as alleviated cell damage by decreasing ROS and apoptosis. It decreased generation of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in PM2.5-induced RAW264.7 and J774A.1 cells. Moreover, coelonin markedly inhibited upregulating the expression of toll-like receptor (TLR)4 and cyclo-oxygenase (COX)-2, blocked activation of p-nuclear factor-kappa B (NF-kappa B) signaling pathway, and suppressed expression of NLRP3 inflammasome, ASC, GSDMD, IL-18 and IL-1 beta. In conclusion, the results showed that coelonin could protect against PM2.5-induced macrophage damage via suppressing TLR4/NF-kappa B/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro.

Automated summary

This study focused on the effect of coelonin on PM2.5-induced macrophage damage. It was found that coelonin could alleviate cell damage and reduce the production of inflammatory cytokines by suppressing TLR4/NF-kappa B/COX-2 signaling pathway and NLRP3 inflammasome activation.