Costunolide and Dehydrocostus Lactone as Inhibitors of Killing Function of Cytotoxic T Lymphocytes

Citations Over Time

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.

Related Papers

• → Molecular analyses of a five-amino-acid cytotoxic T-lymphocyte (CTL) epitope: an immunodominant region which induces nonreciprocal CTL cross-reactivity(1989)138 cited
• → IL-15 stimulates the expansion of AIDS virus-specific CTL(1996)108 cited
• → Individual differences in the orientation of the cytolytic T cell response against mouse tumor P815(1995)48 cited
• → CTL and Equivalent Sublanguages of CTL(1997)18 cited
• → The functional transformation of cytotoxic lymphocytes into T-suppressors under the influence of two mediators(1997)6 cited