Differential regulation of c-Jun N-terminal kinase and NF-kappaB pathway by caffeic acid phenethyl ester in astroglial and monocytic cells.
Caffeic acid phenethyl ester (CAPE), an active component of propolis extracts, has been known for its specific inhibition of nuclear factor kappaB (NF-kappaB) and subsequent anti-inflammatory activity. In this study, we report that (i) CAPE exerts its anti-inflammatory action (inhibition of tumor necrosis factor-induced expression of intercellular adhesion molecule-1 and CC chemokine ligand-2) via NF-kappaB inhibition by two distinct molecular mechanisms in a cell-specific manner: CAPE inhibited downstream pathways of inhibitor kappaB (IkappaB) degradation in monocytic cells, while activation of upstream IkappaB kinase was suppressed by CAPE pre-treatment in astroglial cells; and (ii) CAPE paradoxically activates the c-Jun N-terminal kinase (JNK) pathway, which might be responsible for its pro-apoptotic action and divergent regulation of proinflammatory mediators such as CXC chemokine ligand-8.
Choi
Kyungsun
K
Laboratory of Computational Cell Biology, Department of Bio and Brain Engineering, KAIST, Daejeon, Korea.
Choi
Chulhee
C
D001253:Astrocytes / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects*; D016328:NF-kappa B / Q000378:metabolism*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D048031:JNK Mitogen-Activated Protein Kinases; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol