Dihydro-N-caffeoyltyramine down-regulates cyclooxygenase-2 expression by inhibiting the activities of C/EBP and AP-1 transcription factors.
Dihydro-N-caffeoyltyramine (DHCT), a novel phenolic amide isolated from the root bark of Lycium chinense Miller, has potent antioxidative activity and anti-fungal effects. In the present study, we investigated the effects of DHCT on phorbol 12-myristate 13-acetate (PMA)-induced pro-inflammatory protein cyclooxygenase (COX-2) expression in macrophages. Treatment with DHCT suppressed PMA-mediated induction of COX-2 mRNA and protein. PMA-inducible production of PGE2 was inhibited by DHCT in a dose-dependent manner. Transient transfections and electrophoretic mobility shift assays indicated that the inhibitory effects of DHCT were mediated via CCAAT/enhancer-binding protein (C/EBP) and activator protein 1 (AP-1). DHCT reduced PMA-induced C/EBPbeta protein expression and c-jun/c-fos gene and protein expression. Furthermore, DHCT significantly inhibited PMA-induced activation of the mitogen activated protein (MAP) kinases (ERK and JNK). Thus, DHCT is an effective agent to attenuate COX-2 production mediated by the transcription factors C/EBP and AP-1, and these results enhance our understanding of the anti-inflammatory and anti-cancer properties by DHCT.
Han
Eun Hee
EH
College of Pharmacy, Chungnam National University, Daejeon 305-764, Republic of Korea.
Kim
Ji Young
JY
Kim
Hyung Gyun
HG
Choi
Jae Ho
JH
Im
Ji Hye
JH
Woo
Eun Rhan
ER
Jeong
Hye Gwang
HG
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D004790:Enzyme Induction / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D032305:Lycium / Q000737:chemistry*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014439:Tyramine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000975:Antioxidants; D022762:CCAAT-Enhancer-Binding Proteins; D002109:Caffeic Acids; D010936:Plant Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C472079:dihydro-N-caffeoyltyramine; C016658:phorbolol myristate acetate; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate; D014439:Tyramine