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 Ca2+-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-gamma. 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-kappa B. BAPTA-AM, a chelator of the intracellular calcium, remained without any effect on the secretion of IFN-gamma triggered by TB. These results demonstrate that TB is a potent immunostimulatory agent. (C) 2010 Elsevier B.V. All rights reserved.