Background Spontaneous bacterial peritonitis (SBP) - a severe complication of liver cirrhosis - is driven by bacterial translocation. Bacterial translocation is promoted by immune dysfunctions, increased intestinal permeability and bacterial overgrowth in patients with liver cirrhosis. However, the detailed mechanism of SBP development is still unknown. With wide-ranging function in immunity and cellular stress response, involvement of the p53 family in liver cirrhosis and SBP is conceivable. We studied the regulation of p53 family members and their target functions in an in vitro model and intestinal biopsies of patients with liver cirrhosis.
Methods Intestinal biopsies of 19 controls and 9 patients with liver cirrhosis (5x child-pugh A, 4x child-pugh C) were included in the study. For analysis of the p53 family, mRNA and protein levels of p53 and p73 were analyzed. We established an intestinal in vitro model with the epithelial cell line HCT-116. To mimic bacterial overgrowth, HCT-116 cells were cocultured with Escherichia coli (E. coli) at different concentrations for up to 4 hours. Regulation of p53 and p73 was studied using qPCR and Western blot. Additionally, p53 family target functions were analyzed via cell death induction upon bacterial stimulation.
Results Compared to controls, patients with advanced liver cirrhosis showed a diminished p53 and p73 status on RNA and protein level. In accordance, coincubation of HCT-116 cells with E. coli resulted in a decrease of p53 and p73 protein levels in a time- and dose-dependent manner. Despite reduced levels of p53 family members, high rates of cell death after E. coli stimulation were observed.
Conclusion Advanced liver cirrhosis is accompanied with reduced intestinal expression of p53 family members. Active bacteria trigger these reductions and this mechanism might contribute to prolonged bacterial replication and SBP development. To antagonize a high bacterial burden, intestinal epithelial cells induce cell death. In summary, there is a new role of p53 regulation in bacterial infection like SBP.
