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
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.