Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic T lymphocytes.
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.
Department of Bioengineering, Tokyo Institute of Technology, Yokohama, Japan.
M
M
Taniguchi
T
T
Kataoka
H
H
Suzuki
M
M
Uramoto
M
M
Ando
K
K
Arao
J
J
Magae
T
T
Nishimura
N
N
Otake
K
K
Nagai
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D007783:Lactones / Q000494:pharmacology*; D010766:Phosphorylation; D012717:Sesquiterpenes / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D007783:Lactones; D012717:Sesquiterpenes; C097581:mokko lactone; C014096:alpha-methylene gamma-butyrolactone; D014443:Tyrosine; C083030:dehydrocostus lactone; C002602:costunolide; D015107:4-Butyrolactone