Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent manner.
Lck is a T cell-restricted Src family protein tyrosine kinase that plays pivotal roles in TCR-mediated signaling. We aimed to identify novel agents that could disrupt the molecular interaction of the Src homology 2-domain of Lck (Lck SH2) with its binding partners, with the expectation that this would impair TCR signaling and generate immunosuppression. Large-scale screening of plant extracts indicated that rosmarinic acid (RosA) in extracts of Prunella vulgaris consistently inhibits the interaction between Lck SH2 and a peptide containing its consensus binding sequence (pYEEI). The inhibitory effect of RosA was specific for SH2 domains of Src family protein tyrosine kinase. RosA inhibited TCR-induced-Ca(2+) mobilization and IL-2 promoter activation but not phorbol 12-myristate 13-acetate/ionomycin-induced IL-2 promoter activation, indicating its point of inhibition at the membrane proximal site of TCR signaling. Furthermore, RosA inhibited TCR-induced splenocyte proliferation as well as one-way MLR at an IC(50) of 25-50 microM and inhibited cytokine expression such as IL-2 and IFN-gamma. Here, we first report RosA as an inhibitor of TCR-signaling and subsequent T cell proliferation.[1]References
- Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent manner. Won, J., Hur, Y.G., Hur, E.M., Park, S.H., Kang, M.A., Choi, Y., Park, C., Lee, K.H., Yun, Y. Eur. J. Immunol. (2003) [Pubmed]
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