title: Downregulation of mPGES-1 Expression via EGR1 Plays an Important Role in Inhibition of Caffeine on PGE2 Synthesis of HBx(+) Hepatocytes.
abstract: We investigated the mechanism of caffeine in influencing HBx(+) hepatocytes to synthesize PGE2. The inhibitory effect of caffeine on hepatocyte proliferation increased with increasing caffeine concentrations (200-800 μM) 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 μM caffeine and at caffeine treatment for 7 days. The PGE2 secretion and the expression of mPGES-1 and EGR1 were downregulated, whereas PPARγ 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 PPARγ 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 PPARγ and furthermore affecting the mPGES-1 expression by EGR1 in HBx(+) hepatocytes. The results indicate that caffeine could effectively reduce PGE2 synthesis in HBx(+) hepatocytes by specifically blocking the PPARγ-EGR1-mPGES-1 pathway, thereby providing a new evidence of molecular biology for the hypothesis that drinking coffee is beneficial to HBV-infected patients.
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Fujian Institute of Hepatobiliary Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou 350001, China ; Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Research Center for Molecular Medicine, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Nanhong
authors.initials: N
authors.lastname: Tang
mesh_terms: D002110:Caffeine / Q000737:chemistry*; D002460:Cell Line; D049109:Cell Proliferation; D015232:Dinoprostone / Q000378:metabolism*; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D000071876:Prostaglandin-E Synthases; D015534:Trans-Activators / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D010726:Phosphodiesterase Inhibitors; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D002110:Caffeine; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone