Details

Autor(en) / Beteiligte

• Kim, Young-Dae
• Choi, Suck-Chei
• Oh, Tae-Young
• Chun, Jang-Soo
• Jun, Chang-Duk

Titel

Eupatilin inhibits T-cell activation by modulation of intracellular calcium flux and NF-κB and NF-AT activity

Ist Teil von

• Journal of cellular biochemistry, 2009-09, Vol.108 (1), p.225-236

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Wiley Blackwell Single Titles

Beschreibungen/Notizen

• Eupatilin, one of the pharmacologically active ingredients of Artemisia princeps, exhibits a potent anti‐ulcer activity, but its effects on T‐cell immunity have not been investigated. Here, we show that eupatilin has a profound inhibitory effect on IL‐2 production in Jurkat T cells as well as in human peripheral blood leukocytes. Eupatilin neither influenced clustering of CD3 and LFA‐1 to the immunological synapse nor inhibited conjugate formation between T cells and B cells in the presence or absence of superantigen (SEE). Eupatilin also failed to inhibit T‐cell receptor (TCR) internalization, thereby, suggesting that eupatilin does not interfere with TCR‐mediated signals on the membrane proximal region. In unstimulated T cells, eupatilin significantly induced apoptotic cell death, as evidenced by an increased population of annexin V+/PI+ cells and cleavage of caspase‐3 and PARP. To our surprise, however, once cells were activated, eupatilin had little effect on apoptosis, and instead slightly protected cells from activation‐induced cell death, suggesting that apoptosis also is not a mechanism for eupatilin‐induced T‐cell suppression. On the contrary, eupatilin dramatically inhibited I‐κBα degradation and NF‐AT dephosphorylation and, consequently, inhibited NF‐κB and NF‐AT promoter activities in PMA/A23187‐stimulated T cells. Interestingly, intracellular calcium flux was significantly perturbed in cells pre‐treated with eupatilin, suggesting that calcium‐dependent cascades might be targets for eupatilin action. Collectively, our results provide evidence for dual regulatory functions of eupatilin: (1) a pro‐apoptotic effect on resting T cells and (2) an immunosuppressive effect on activated T cells, presumably through modulation of Ca2+ flux. J. Cell. Biochem. 108: 225–236, 2009. © 2009 Wiley‐Liss, Inc.