Phytocomponent p-Hydroxycinnamic acid inhibits T-cell activation by modulation of protein kinase C-θ-dependent pathway

The phytocomponent p-hydoxycinnamic acid (HCA) has been shown to have many beneficial effects in terms of antioxidant activity, inhibition of melanogenesis, bone resorption, and platelet activity, and stimulation of mineralization. However, effects of HCA in immune functions have not been investigated. Here, we show that HCA has a profound effect on IL-2 production in Jurkat T cells as well as in human peripheral blood leukocytes. HCA, at a concentration that optimally inhibits IL-2 production, had little effect on apoptotic or necrotic cell death of Jurkat T cells, suggesting that apoptosis is not a mechanism for HCA-induced T-cell suppression. On the contrary, HCA dramatically inhibited PKC-θ accumulation and further phosphorylation at the immunological synapse which formed at the contact site between T cells and superantigen SEE-loaded antigen presenting cells. In addition, HCA significantly inhibited ERK and p38 kinase phosphorylation in both anti-CD3/28- and PMA/A23187-stimulated T cells. Consequently, HCA inhibited both AP-1 and NF-κB promoter activities in Jurkat T cells. Collectively, our results provide evidence for the immunosuppressive effect of HCA on activated T cells, through modulation of PKC-θ pathway.