European journal of immunology, 2003-04, Vol.33 (4), p.870-879
2003
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Rosmarinic acid inhibits TCR‐induced T cell activation and proliferation in an Lck‐dependent manner
- Ist Teil von
- European journal of immunology, 2003-04, Vol.33 (4), p.870-879
- Ort / Verlag
- Weinheim: WILEY‐VCH Verlag
- Erscheinungsjahr
- 2003
- Quelle
- Wiley Online Library Journals Frontfile Complete
- Beschreibungen/Notizen
- 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 interactionof 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0014-2980eISSN: 1521-4141DOI: 10.1002/eji.200323010Titel-ID: cdi_proquest_miscellaneous_73157849
- Format
- –
- Schlagworte
- Calcium - metabolism, Cells, Cultured, Cinnamates - chemistry, Cinnamates - pharmacology, Cytokines - metabolism, Depsides, Enzyme-Linked Immunosorbent Assay, Humans, Interleukin-2 - genetics, Ion Transport - drug effects, Jurkat Cells, Lck, Lymphocyte Activation - drug effects, Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - chemistry, Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - physiology, Phosphopeptides - metabolism, Phosphorylation, Promoter Regions, Genetic, Protein-Tyrosine Kinases - metabolism, Prunella vulgaris, Receptors, Antigen, T-Cell - antagonists & inhibitors, Rosa, Rosmarinic Acid, Spleen - immunology, Src homology 2, src Homology Domains, Surface Plasmon Resonance, T-Lymphocytes - drug effects, T-Lymphocytes - enzymology, T-Lymphocytes - immunology, TCR signaling, Transcriptional Activation, ZAP-70 Protein-Tyrosine Kinase