title: Tumor necrosis factor-induced activation of peritoneal macrophages is regulated by prostaglandin E2 and cAMP.
abstract: Human rTNF-alpha stimulates the metabolism of murine peritoneal macrophages as demonstrated by an increased consumption of arginine and an increased release of L-ornithine. This TNF-mediated effect is augmented by several substances that raise the intracellular concentration of cAMP, including PGE2, cholera toxin, and dibutyryl-cAMP. TNF also stimulates the endogenous production of PGE2 in cultures of peritoneal macrophages. The addition of the cyclo-oxygenase inhibitor, indomethacin, suppresses the TNF-mediated metabolic activation of macrophages, and this suppressive effect of indomethacin is overcome if exogenous PGE2 or cholera toxin is added to the culture. Taken together, the experiments indicate that the TNF-induced production of PGE2 and the PGE2-induced increase of the intracellular cAMP concentration are essential elements of an auto-regulatory loop that controls the magnitude of the TNF-mediated effect in the macrophage.
authors.affiliation: Deutsches Kresbsforschungszentrum Institut für Immunologie und Genetik, Heidelberg, Federal Republic of Germany.
authors.forename: V
authors.initials: V
authors.lastname: Lehmmann
authors.forename: B
authors.initials: B
authors.lastname: Benninghoff
authors.forename: W
authors.initials: W
authors.lastname: Dröge
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002772:Cholera Toxin / Q000494:pharmacology; D015232:Dinoprostone; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D011458:Prostaglandins E / Q000096:biosynthesis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D003994:Bucladesine; D002772:Cholera Toxin; D015232:Dinoprostone