1. Academic Validation
  2. Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic T lymphocytes

Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic T lymphocytes

  • Biosci Biotechnol Biochem. 1995 Nov;59(11):2064-7. doi: 10.1271/bbb.59.2064.
M Taniguchi 1 T Kataoka H Suzuki M Uramoto M Ando K Arao J Magae T Nishimura N Otake K Nagai
Affiliations

Affiliation

  • 1 Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
Abstract

Costunolide and dehydrocostus lactone were isolated from an extract of mokko (Saussurea lappa Clarke) as inhibitors of killing activity of cytotoxic T lymphocytes (CTL). Mokko lactone was also isolated as an inactive compound from the extract. The structure-activity relationship indicated that alpha-methylene-gamma-butyrolactone is required for the inhibitory effect. Costunolide markedly inhibited the granule exocytosis and the production of inositol phosphates in response to anti-CD3 monoclonal antibody (mAb) stimulation at a concentration that did not affect the binding of anti-CD3 mAb. Tyrosine phosphorylation induced by crosslinking of CD3 molecules was significantly inhibited by costunolide in a dose-dependent manner. These results suggest that costunolide inhibits the killing activity of CTL through preventing the increase in tyrosine phosphorylation in response to the crosslinking of T-cell receptors.

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