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.
Peters
T
T
Biochemisches Institut, Albert-Ludwigs-Universität, Freiburg, Federal Republic of Germany.
Gaillard
T
T
Decker
K
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone / Q000096:biosynthesis*; D007700:Kinetics; D007728:Kupffer Cells / Q000378:metabolism*; D008297:Male; D015230:Prostaglandin D2 / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D013929:Thromboxane B2; D015232:Dinoprostone; D015230:Prostaglandin D2