Inhibitory effect and underlying mechanism of hepatocytes on bacterial proliferation

Abstract

Objective To explore the role and mechanism of hepatocytes in inhibiting bacterial proliferation by phagocytizing bacteria directly and mediating the expression of antibacterial proteins indirectly. Methods Cellular model of Escherichia coli (E.coli) infection was established in normal murine hepatocyte line FL83B and mouse Kupffer cells to determine the effects of the cells on the proliferation of bacteria. After the bacteria were co-cultured with Kupffer/FL83B cells and the 6-, 12-, and 24-hour supernatants, respectively, the lethality of E. coli was determined for the direct bacteriostatic effect of the hepatocytes. The phagocytizing ability of FL83B cells were measured with phagocytosis reagent kit. qRT-PCR and Western blotting were employed to detect the expression of related molecules at mRNA and protein levels. Results When the hepatocyte were incubated with E. coli, FL83B cells, as Kupffer cells, could directly inhibit the proliferation of the bacteria (P < 0.05) and maintained a high survival rate at same time. Phagocytic function test showed that FL83B cells could directly phagocytize bacterial particles. Compared with the FL83B cells without E. coli infection, the mRNA levels of phagocytosis-related genes Fcgr1, Marco, Cdc42, and RhoB were increased, that of antigen presentation related gene β2M was also upregulated, the NF-κB, MAPK, and STAT3 signaling pathways were activated, and the protein levels of antibacterial-related proteins iNOS, NOX2, and RhoB were also enhanced in the cells after infection (all P < 0.05). Conclusion Mouse FL83B hepatocytes possess the ability to inhibit bacteria through direct phagocytosis and indirect upregulation of antibacterial-related proteins.

Keywords

• hepatocytes
• bacterial infection
• phagocytosis