title: Phytocomponent p-Hydroxycinnamic acid inhibits T-cell activation by modulation of protein kinase C-θ-dependent pathway.
abstract: 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.
authors.affiliation: 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.
authors.forename: Hyun-Su
authors.initials: HS
authors.lastname: Lee
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Bo-Ra
authors.initials: BR
authors.lastname: Na
authors.forename: Hye-Ran
authors.initials: HR
authors.lastname: Kim
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Choi
authors.forename: Weon-Cheol
authors.initials: WC
authors.lastname: Han
authors.forename: Hyun-Kyu
authors.initials: HK
authors.lastname: Choi
authors.forename: Seung-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Chang-Duk
authors.initials: CD
authors.lastname: Jun
mesh_terms: D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear; D016328:NF-kappa B / Q000378:metabolism; D011422:Propionates; D011493:Protein Kinase C / Q000378:metabolism*; D000074121:Protein Kinase C-theta; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D003373:Coumaric Acids; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007527:Isoenzymes; D016328:NF-kappa B; D011422:Propionates; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C495469:p-coumaric acid