Nonlinear proinflammatory effect of short-term PM_2.5 exposure: A potential role of lipopolysaccharide

The association between PM_2.5 (particulate matter ≤ 2.5 µm) short-term exposure and its health effect is non-linear from the epidemiological studies. And this nonlinearity is suggested to be related with the PM_2.5 heterogeneity, however, the underlying biological mechanism is still unclear. Here, a total of 38 PM_2.5 filters were collected continuously for three weeks in winter Beijing, with the ambient PM_2.5 varying between 10 and 270 µg/m³. Human monocytes-derived macrophages (THP-1) were treated with PM_2.5 water-soluble elutes at 10 µg/mL to investigate the PM_2.5 short-term exposure effect from a proinflammatory perspective. The proinflammatory cytokine tumor necrosis factor (TNF) induced by the PM_2.5 elutes at equal concentrations were unequal, showing the heterogeneity of PM_2.5 proinflammatory potentials. Of the various chemical and biological components, lipopolysaccharide (LPS) showed a strong positive association with the TNF heterogeneity. However, some outliers were observed among the TNF-LPS association. Specifically, for PM_2.5 from relatively clean air episodes, the higher LPS amount corresponded to relatively low TNF levels. And this phenomenon was also observed in the promotion tests by treating macrophages with PM_2.5 elutes dosed with additional trace LPS. Gene expression analysis indicated the involvement of oxidative-stress related genes in the LPS signaling pathway. Therefore, a potential oxidative-stress-mediated suppression on the PM_2.5-borne LPS proinflammatory effect was proposed to be accounted for the outliers. Overall, the results showed the differential role of LPS in the heterogeneity of PM_2.5 proinflammatory effects from a component-based perspective. Future experimental studies are needed to elucidate the signaling pathway of LPS attached on PM_2.5 from different air quality episodes.