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

Summary 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.