Tumor necrosis factor alpha stimulates prostaglandin but not superoxide synthesis in rat Kupffer cells

Recombinant mouse TNF-alpha (TNF) stimulated the synthesis of prostaglandin E2, prostaglandin D2 and thromboxane in primary cultures of rat Kupffer cells. Compared to the unstimulated control the 24 h output of these three prostanoids was increased three- to four-fold in a concentration-dependent manner. PGD2-like immunoreactivity was the predominant product, while HPLC analysis of all the prostanoids produced by prelabelled Kupffer cells after TNF stimulation revealed thromboxane and PGE2 (37% each) as the main products. PGD2 was degraded during the incubation period to less polar products, probably PGJ2 and delta 12-PGJ2 that cross-react with the anti-PGD2 antiserum. TNF did not trigger superoxide generation in rat Kupffer cells but it does in neutrophils. The TNF-elicited PGE2 production together with the previously described [Karck, Peters & Decker (1988) J. Hepatol. 7:352-361] inhibition of TNF release by PGE2 in rat Kupffer cells establishes a regulatory circuit of self-limiting TNF production in liver macrophages.