Shikonin suppresses human t lymphocyte activation through inhibition of IKK β activity and JNK phosphorylation

Abstract

The key role of T cells has been elaborated in mediating immune responses and pathogenesis of human inflammatory and autoimmune conditions. In the current study the effect of shikonin, a compound isolated from a medicinal plant, on inhibition of T-cell activation was firstly examined by using primary human T lymphocytes isolated from buffy coat. Results showed that shikonin dose dependently suppressed T-cell proliferation, IL-2 and IFN-γ secretion, CD69 and CD25 expression, as well as cell cycle arrest activated by costimulation of PMA/ionomycin or OKT-3/CD28 monoclonal antibodies. Moreover, these inhibitory responses mediated by shikonin were found to be associated with suppression of the NF-B signaling pathway via inhibition of the IKKα/β phosphorylation, IB-α phosphorylation and degradation, and NF-B nuclear translocation by directly decreasing IKKβ activity. Moreover, shikonin suppressed JNK phosphorylation in the MAPKs pathway of T cells. In this connection, we conclude that shikonin could suppress T lymphocyte activation through suppressing IKKβ activity and JNK signaling, which suggests that shikonin is valuable for further investigation as a potential immunosuppressive agent. © 2013 Ting Li et al.