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-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.

Graphical AbstractFigure optionsDownload as PowerPoint slideImmunostimulatory effect of trilobolide, a sesquiterpene lactone isolated from Laser trilobum is reported and discussed. Trilobolide activates secretion of IFN-γ and NO production in rodent macrophages and human peripheral mononuclear blood cells.