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Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent manner

Title
Rosmarinic acid inhibits TCR-induced T cell activation and proliferation in an Lck-dependent manner
Authors
Won J.Hur Y.-G.Hur E.M.Park S.-H.Kang M.-A.Choi Y.Park C.Lee K.-H.Yun Y.
Ewha Authors
윤영대
SCOPUS Author ID
윤영대scopus
Issue Date
2003
Journal Title
European Journal of Immunology
ISSN
0014-2980JCR Link
Citation
vol. 33, no. 4, pp. 870 - 879
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
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- Ca2+ 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 IC50 of 25-50 μM and inhibited cytokine expression such as IL-2 and IFN-γ. Here, we first report RosA as an inhibitor of TCR-signaling and subsequent T cell proliferation.
DOI
10.1002/eji.200323010
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
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