title: Caffeic acid phenethyl ester inhibits nuclear factor-kappaB and protein kinase B signalling pathways and induces caspase-3 expression in primary human CD4+ T cells.
abstract: Caffeic acid phenethyl ester (CAPE), an active component in propolis, is known to have anti-tumour, anti-inflammatory and anti-oxidant properties. In this study, the effects of CAPE on the functions of primary human CD4+ T cells were evaluated in vitro. CAPE significantly suppressed interferon (IFN)-gamma and interleukin (IL)-5 production and proliferation of CD4+ T cells stimulated by soluble anti-CD3 and anti-CD28 monoclonal antibodies in both healthy subjects and asthmatic patients. CAPE inhibited nuclear factor (NF)-kappaB activation and protein kinase B (Akt) phosphorylation, but not p38 mitogen-activated protein kinase (MAPK) phosphorylation in T cells. CAPE also induced active caspase-3 expression in CD4+ T cells; CCR4+CD4+ T cells were more sensitive to CAPE induction than CXCR3+CD4+ T cells. Together, these results indicate that CAPE inhibits cytokine production and proliferation of T cells, which might be related to the NF-kappaB and Akt signalling pathways, and that CCR4+CD4+ T cells are more sensitive to CAPE inhibition. This study provides a new insight into the mechanisms of CAPE for immune regulation and a rationale for the use of propolis for the treatment of allergic disorders.
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: L-C
authors.initials: LC
authors.lastname: Wang
authors.forename: K-H
authors.initials: KH
authors.lastname: Chu
authors.forename: Y-C
authors.initials: YC
authors.lastname: Liang
authors.forename: Y-L
authors.initials: YL
authors.lastname: Lin
authors.forename: B-L
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D039741:Antigens, Dermatophagoides / Q000009:adverse effects / Q000276:immunology; D001249:Asthma / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D053148:Caspase 3 / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011429:Propolis / Q000737:chemistry; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D054398:Receptors, CCR4 / Q000032:analysis; D054367:Receptors, CXCR3 / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039741:Antigens, Dermatophagoides; C515354:CCR4 protein, human; C515187:CXCR3 protein, human; D002109:Caffeic Acids; D016207:Cytokines; D016328:NF-kappa B; D054398:Receptors, CCR4; D054367:Receptors, CXCR3; D011429:Propolis; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol