INTERFERON-GAMMA STIMULATES PROSTAGLANDIN-E2 PRODUCTION BY MOUSE KUPFFER CELLS

When mononuclear phagocytes, including Kupffer cells, are activated by various agents, they synthesize and release arachidonic acid metabolites, prostaglandins (PGs) and leukotrienes (LTs). In this study, we examined the effect of in vitro Kupffer cell activation with recombinant murine IFNγ on PGE2 and LTB4 secretion. IFNγ enhanced PGE2 secretion, and this effect of IFNγ was stronger than that of IL-1 or TNF. Moreover, IFNγ promoted LTB4 release especially in the absence of PGs. On the other hand, dexamethasone and indomethacin inhibited and, EGTA and TMB-8, which reduce intracellular Ca++ Levels, blocked IFNγ induced PGE2 production, which suggested that the activation of phospholipase A2 and cyclooxygenase in Kupffer cells requires the elevation of intraceulullar Ca++ levels. © 1990.