PM2.5 promoted lipid accumulation in macrophage via inhibiting JAK2/STAT3 signaling pathways and aggravating the inflammatory reaction

Background: Abnormal lipid accumulation in macrophages may lead to macrophages foaming, which is the most important pathological process of atherosclerosis. Atmospheric PM2.5 could enter the blood circulation and further affect the lipid metabolism of macrophages. But the underlying mechanism is not unclear. This study was undertaken to clarify the effect of PM2.5 on lipid metabolism in macrophages, and to explore the role of inflammatory reaction and JAK2/STAT3 signaling pathway in this process. Method: Macrophages derived from THP-1 cells were exposed to PM2.5 (0,100,200,400 mu g/mL) for 6 h and 12 h. STAT3 agonist ColivelinTFA is used to specifically excite STAT3. The survival rate of macrophages was detected by CCK-8. The lipid levels in macrophages were detected by colorimetry. The levels of inflammatory factors secreted by macrophages were detected by ELISA. Q-PCR was used to detect the mRNA expression levels, and Western Blot was used to detect the protein expression levels of JAK2/STAT3 pathway genes. Result: The survival rate of macrophages was reduced by PM2.5, and the levels of TG, T-CHO and LDL-C of macrophages exposed to PM2.5 were increased. PM2.5 led to the increasing level of IL-6 and the decreasing level of IL-4, and the JAK2/STAT3 signaling pathway was inhibited by PM2.5. Colivelin TFA significantly decreased the increasing levels of TG, T-CHO and LDL-C levels, and increased the decreasing mRNA levels of IL-4, and LPL induced by PM2.5 (p < 0.05). Discussion: PM2.5 could cause the lipid accumulation of macrophages by inhibiting the JAK2/STAT3 signaling pathway, and inflammatory responses may be involved in this process.

Automated summary

This study showed that exposure to PM2.5 could lead to abnormal lipid metabolism and inflammatory responses in macrophages, with inhibition of the JAK2/STAT3 signaling pathway. Activation of STAT3 could reverse these effects.