School of Life Sciences, Immune Synapse Research Center and Cell Dynamics Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Republic of Korea.
Int Immunopharmacol. 2012 Jan;12(1):131-8. doi: 10.1016/j.intimp.2011.11.001. Epub 2011 Nov 17.
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.
植物成分对羟基肉桂酸（HCA）已被证明在抗氧化活性、黑色素生成抑制、骨吸收、血小板活性抑制和矿化刺激方面具有许多有益作用。然而，HCA 对免疫功能的影响尚未得到研究。在这里，我们表明 HCA 对 Jurkat T 细胞和人外周血白细胞中的 IL-2 产生有深远影响。在最佳抑制 IL-2 产生的浓度下，HCA 对 Jurkat T 细胞的凋亡或坏死性细胞死亡几乎没有影响，这表明凋亡不是 HCA 诱导 T 细胞抑制的机制。相反，HCA 显著抑制了在 T 细胞与超抗原 SEE 加载的抗原呈递细胞接触部位形成的免疫突触处 PKC-θ 的积累和进一步磷酸化。此外，HCA 还显著抑制了抗 CD3/28 和 PMA/A23187 刺激的 T 细胞中 ERK 和 p38 激酶的磷酸化。因此，HCA 抑制了 Jurkat T 细胞中 AP-1 和 NF-κB 启动子的活性。总之，我们的结果提供了证据表明 HCA 通过调节 PKC-θ 途径对活化的 T 细胞具有免疫抑制作用。
