Caffeic acid phenethyl ester inhibits nuclear factor-κB and protein kinase B signalling pathways and induces caspase-3 expression in primary human CD4⁺ T cells

• Published in: Clinical and experimental immunology Vol. 160; no. 2; pp. 223 - 232
• Main Authors: Wang, L.-C, Chu, K.-H, Liang, Y.-C, Lin, Y.-L, Chiang, B.-L
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.05.2010; Blackwell Publishing Ltd; Blackwell; Blackwell Science Inc
• Subjects: Akt; Analytical, structural and metabolic biochemistry; Biological and medical sciences; caffeic acid phenethyl ester; caspase-3; CD4+ T cells; CD4⁺ T cells; Fundamental and applied biological sciences. Psychology; NF-κB; Translational Studies; Human; CD4 T lymphocyte; Enzyme; Cysteine endopeptidases; Akt protein kinase; Biochemistry; Akt; T cells; Caffeic acid; Peptidases; Ester; NF-κB; CD4; Signaling pathway; Primary; caffeic acid phenethyl ester; Hydrolases; Inhibitor; Transcription factor NFκB; caspase-3
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/j.1365-2249.2009.04067.x

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)-γ 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)-κB 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-κB 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.