PM2.5 Exposure Induces Inflammatory Response in Macrophages via the TLR4/COX-2/NF-κB Pathway

Abstract

Fine particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) is a serious air pollutant associated with health problems. Macrophages play an important role in the process of PM2.5-induced inflammation in respiratory diseases. However, the detailed mechanism remains unclear. We aimed to examine the mechanism of PM2.5-induced inflammation and find possible anti-inflammatory inhibitors. PM2.5 was collected in Hangzhou, China, and the composition of adsorbed materials on PM2.5 was characterized. RAW 254.7 cells were then treated with PM2.5. Phagocytosis was observed, and inflammatory response was triggered as demonstrated by the release of high levels of monocyte chemoattractant protein-1(MCP-1), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and increased mRNA expression of inducible nitric oxide synthase (iNOS) and TNF-α. Treatment with classic inhibitors suppressed the released pro-inflammatory factors in a dose-dependent manner. Using Immunology Inflammation Compound Library, we screened 70 inhibitors and clustered them based on similarities in their inhibitory effects, which we detected using cytometric bead array (CBA) assay. Molecular analysis revealed that the expression of toll-like receptor 4 (TLR4), nuclear factor kappa-B (NF-κB), and cyclooxygenase-2 (COX-2) was increased in PM2.5-stimulated RAW 254.7 cells. Corresponding inhibitors were selected, and the CBA assay verified their anti-inflammatory effects. These inhibitors reduced the expression of pro-inflammatory factors, and this reduction was correlated with the downregulation of the TLR4/NF-κB/COX-2 signaling pathway. In conclusion, PM2.5 induces an inflammatory response in macrophages via activation of TLR4/NF-κB/COX-2 signaling, and the inhibitors of this pathway are potential therapeutic candidates to treat inflammatory disorders.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant Numbers 81673672, 81673645, 81873047, and 81573677) and Natural Science Foundation of Zhejiang Province (Grant Numbers LQ17H030006).

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Correspondence to Qiyang Shou or Zhishan Ding.

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Fu, H., Liu, X., Li, W. et al. PM2.5 Exposure Induces Inflammatory Response in Macrophages via the TLR4/COX-2/NF-κB Pathway. Inflammation (2020). https://doi.org/10.1007/s10753-020-01269-y

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KEY WORDS

  • PM2.5
  • macrophages
  • inflammation
  • TLR4
  • NF-κB
  • COX-2