Repeated exposure to fine particulate matter constituents lead to liver inflammation and proliferative response in mice

Fine particulate matter (particulate matter with aerodynamic diameter of ≦2.5 µm, PM2.5) exposure cause adverse health effects, including lung inflammation. Through intra-tracheal instillation of PM2.5 components, the study aimed to evaluate the inflammatory and proliferative effects on mice liver. PM2.5 samples were collected near an industrial complex at southern Taiwan. Mice were exposed to water extracts or insoluble particles by intra-tracheal instillation. Male C57BL/6 mice were divided into five groups: control, low dose insoluble particle exposure (LP), high dose insoluble particle exposure (HP), low dose water extract exposure (LW), and high dose water extract exposure (HW). Biochemical analysis, western blotting, histological examination, and immunohistochemistry were employed to evaluate the results. Enrichment factor (EF) of metallic elements showed that the EFs of trace elements (Ti, V, Ni, Zn, Pb, Cr, and Cu) in PM2.5 were above 10. Hematoxylin and Eosin (H&E) staining of the liver tissue showed inflammatory infiltration in particle exposure group; hepatocyte ballooning degeneration and karyomegaly were seen in the water extract exposure group. Upregulation of inflammatory signaling, p65 and p50, and caspase-3 (an important effector involved in apoptosis) positive hepatocytes was significantly increased in the HP group, followed by an elevation in protein levels of growth arrest and DNA damage-inducible protein 153 (GADD153). Increased protein expression of proliferating cell nuclear antigen (PCNA) was noted in the LW and HW groups. An increase in phosphorylation of regulators of cell proliferation, Akt and extracellular signal-regulated kinase (ERK) 1/2, were detected in the LW and HW groups. The present study shows that the insoluble particle composition of PM2.5 induced inflammatory signaling and cytokines upregulation in the liver, accompanied with inflammatory cell and macrophage infiltration and an abnormal liver function. Exposure of water extract to PM2.5 induced signals of upregulated cellular proliferation, elevated markers of cell proliferation in liver, hepatocyte ballooning degeneration and karyomegaly.