PROSTANOIDS INHIBIT KUPFFER CELL NITRIC-OXIDE SYNTHESIS

Kupffer cells are the largest population of fixed tissue macrophages i n the body and produce a number of mediators that are involved in host defense. These mediators include cytokines such as tumor necrosis fac tor-alpha and interleukin-1, prostaglandins, oxygen radicals, and nitr ic oxide. Prostaglandins are produced by adjacent endothelial cells in addition to Kupffer cells and regulate a number of cellular functions in a wide array of cells, but their role in nitric oxide synthesis is controversial. We studied the role of prostaglandins in regulating li popolysaccharide (LPS)-induced nitric oxide synthesis in cultured rat Kupffer cells. Prostaglandin E(2) (PGE(2)) inhibited Kupffer cell nitr ic oxide synthesis in a dose-dependent fashion in both 24- and 48-hr c ultures. The effect of PGE(2) persisted at low and high LPS concentrat ions. Prostaglandin analogues as well as other prostanoids also inhibi ted Kupffer cell nitric oxide synthesis. These data show that exogenou s prostaglandins suppress Kupffer cell nitric oxide synthesis and may represent an important endogenous regulator of nitric oxide production . (C) 1995 Academic Press, Inc.