Downregulation of mPGES-1 Expression via EGR1 Plays an Important Role in Inhibition of Caffeine on PGE(2) Synthesis of HBx(+) Hepatocytes

作者：Ma, Yan; Wang, Xiaoqian; Tang, Nanhong^*

来源：Mediators of Inflammation, 2015, 2015: 372750.

DOI：10.1155/2015/372750

• HEPATOCELLULAR-CARCINOMA
• CELLS
• GROWTH
• PROLIFERATION
• APOPTOSIS
• INVASION
• GAMMA

We investigated the mechanism of caffeine in influencing HBx(+) hepatocytes to synthesize PGE(2). The inhibitory effect of caffeine on hepatocyte proliferation increased with increasing caffeine concentrations (200-800 mu M) and treatment times (1-7 days), which was first observed at the second test time point (caffeine treatment for 4 days). The inhibition of caffeine on the growth of HL7702-HBx and HepG2-HBx cells was most obvious at 800 mu M caffeine and at caffeine treatment for 7 days. The PGE(2) secretion and the expression of mPGES-1 and EGR1 were downregulated, whereas PPAR gamma expression was upregulated. The mPGES-1 promoter activity of HBx(+) hepatocytes decreased more significantly than that of HBx(-) hepatocytes. Moreover, the expression of EGR1 and PPAR gamma changed more significantly in HBx(+) hepatocytes cultured for 12 to 24 hours in the presence of 5 mM caffeine. This limited success may be attributed to caffeine releasing the binding of HBx and PPAR gamma and furthermore affecting the mPGES-1 expression by EGR1 in HBx(+) hepatocytes. The results indicate that caffeine could effectively reduce PGE(2) synthesis in HBx(+) hepatocytes by specifically blocking the PPAR gamma-EGR1-mPGES-1 pathway, thereby providing a new evidence of molecular biology for the hypothesis that drinking coffee is beneficial to HBV-infected patients.

• 出版日期2015
• 单位福建医科大学