Sesquiterpene lactone trilobolide activates production of interferon-γ and nitric oxide.
Trilobolide (TB), a sesquiterpene lactone isolated from Laser trilobum is an inhibitor of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA). We have found that upon the in vitro exposure to TB, rodent peritoneal cells and human peripheral blood mononuclear cells secrete high amounts of IFN-γ. The effect is associated with the stimulation of high output NO biosynthesis in rat cells. The stimulatory potential of TB depends on the activation of MAP kinases p38 and ERK1/2, and transcription factor NF-κB. BAPTA-AM, a chelator of the intracellular calcium, remained without any effect on the secretion of IFN-γ triggered by TB. These results demonstrate that TB is a potent immunostimulatory agent.
Kmoníčková
Eva
E
Department of Pharmacology, Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, vvi, Prague, Czech Republic. kmonickova@biomed.cas.cz
Harmatha
Juraj
J
Vokáč
Karel
K
Kostecká
Petra
P
Farghali
Hassan
H
Zídek
Zdeněk
Z
D000818:Animals; D002087:Butyrates / Q000737:chemistry* / Q000494:pharmacology*; D002470:Cell Survival; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D010537:Peritoneum / Q000166:cytology; D051381:Rats; D011917:Rats, Inbred Lew
D002087:Butyrates; D005663:Furans; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D009569:Nitric Oxide; C086352:trilobolide; D004533:Egtazic Acid; D007371:Interferon-gamma