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
  • 1. Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
PMID: 8541643 DOI: 10.1271/bbb.59.2064
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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