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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Dermatophagoides / adverse effects
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Antigens, Dermatophagoides / immunology
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Asthma / etiology
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Asthma / immunology*
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Asthma / pathology
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CD4-Positive T-Lymphocytes / chemistry
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CD4-Positive T-Lymphocytes / drug effects*
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CD4-Positive T-Lymphocytes / enzymology
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CD4-Positive T-Lymphocytes / metabolism
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Caffeic Acids / pharmacology*
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Caspase 3 / biosynthesis*
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Caspase 3 / genetics
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Cells, Cultured / drug effects
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Cytokines / metabolism
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Drug Evaluation, Preclinical
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Enzyme Activation / drug effects
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Enzyme Induction / drug effects
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Humans
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Lymphocyte Activation / drug effects
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NF-kappa B / antagonists & inhibitors*
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Phenylethyl Alcohol / analogs & derivatives*
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Phenylethyl Alcohol / pharmacology
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Phosphorylation / drug effects
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Propolis / chemistry
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Protein Processing, Post-Translational / drug effects
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
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Receptors, CCR4 / analysis
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Receptors, CXCR3 / analysis
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Signal Transduction / drug effects*
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T-Lymphocyte Subsets / chemistry
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T-Lymphocyte Subsets / drug effects*
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T-Lymphocyte Subsets / enzymology
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T-Lymphocyte Subsets / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Antigens, Dermatophagoides
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CCR4 protein, human
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CXCR3 protein, human
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Caffeic Acids
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Cytokines
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NF-kappa B
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Receptors, CCR4
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Receptors, CXCR3
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Propolis
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Proto-Oncogene Proteins c-akt
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p38 Mitogen-Activated Protein Kinases
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Caspase 3
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caffeic acid phenethyl ester
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Phenylethyl Alcohol