Abstract: Objective To investigate the effect of prostaglandin E2 (PGE2) on hepatitis B virus (HBV) replication and T cell function.Methods The concentrations of PGE2 in serum of chronic hepatitis B (CHB) patients and healthy persons (HP) were measured by enzyme-linked immunosorbent assay. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of patients with high or low levels of PGE2 were detected by kit,according to the instructions from the manufacturers. Flow cytometry was used to detect the function of cluster of differentiation 8⁺T cell (CD8⁺T cell) in blood samples. A total of 24 mice injected with recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome via tail vein were randomly divided into 3 groups: control group (dimethylsulfoxide), PGE2 group (stable analog of PGE2) and PGE2 receptor antagonist group (PGE2 receptor antagonist). The levels of hepatitis B surface antigen (HBsAg), HBV deoxyribonucleic acid (DNA) and pregenomic ribonucleic acid (pgRNA) in mouse serum of the 3 groups were detected by kit and real-time quantitative polymerase chain reaction. The function of CD8⁺ T cell in the liver were detected by flow cytometry. Results The serum level of PGE2 in CHB patients was significantly higher than that in HP (877.2 ± 43.27 vs. 201.3 ± 13.38, P<0.05). In patients with high PGE2, the serum levels of HBV DNA, ALT, AST were significantly higher than those in patients with low PGE2 (1.84 ± 0.161 vs. 0.92 ± 0.143, 722.64 ± 33.081 vs. 246.95 ± 26.629, 514.20 ± 13.427 vs. 183.07 ± 12.259, P<0.05), and the expression of T cell immunoglobulin and mucin domain 3 in blood CD8⁺ T cells (Tim3) was significantly higher (18.64 ± 2.051 vs. 15.12 ± 2.265, P<0.05), the expression of granzyme B was significantly lower than that in patients with low PGE2 (0.29 ± 0.102 vs. 0.38 ± 0.095, P<0.05). Compared with the control group, the serum levels of HBsAg, HBV DNA and pgRNA in the PGE2 group were significantly higher (5.57 ± 0.941 vs. 4.51 ± 0.662, 0.58 ± 0.073 vs. 0.42 ± 0.049, 0.57 ± 0.069 vs. 0.40 ± 0.051, P<0.05), the expression of Tim3 in liver CD8⁺ T cells was significantly higher (25.45 ± 3.412 vs. 12.63 ± 2.313, P<0.05), and the expression of tumor necrosis factor-α and interferon-γ was significantly lower in the PGE2 group (21.50 ± 3.139 vs. 27.36 ± 3.841, 15.23 ± 2.105 vs. 24.81 ± 2.595, P<0.05). PGE2 receptor antagonism has the opposite effect.Conclusion PGE2 is highly expressed in serum of CHB patients, which promotes replication of HBV and depletion of T cell. And blocking of PGE2 can not only restore T cell function but also reduce HBV replication.

Key words: Prostaglandin E2, Hepatitis B Virus, Replication, Mechanism