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

Jonghwa Won, Yun Gyoung Hur, Eun Mi Hur, See Hyoung Park, Mi Ae Kang, Youngbong Choi, Changwon Park, Keun Hyeung Lee, Yungdae Yun

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)870-879
Number of pages10
JournalEuropean Journal of Immunology
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

Keywords

  • Lck
  • Rosmarinic acid
  • Src homology 2
  • TCR signaling

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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