title: Tumor necrosis factor alpha is involved in the induction of plasminogen activator inhibitor-1 by endotoxin.
abstract: Treatment with endotoxin leads to a rise in plasminogen activator inhibitor-1 (PAI-1) both in vivo and in vitro. Although a recent study insists that inhibition of tumor necrosis factor alpha (TNF alpha) does not reduce the induction of PAI-1 by endotoxin in rats, we imagine that TNF alpha is involved in the induction of PAI-1 by endotoxin, because endotoxin treatment induces TNF alpha and administration of TNF alpha induces PAI-1 both in vitro and in vivo. In order to confirm this hypothesis, we have measured plasma PAI activity and PAI-1 mRNA in liver after endotoxin treatment with or without pretreatment by polyclonal rabbit antiserum against murine TNF alpha. Chronically cannulated Sprague-Dawley rats received intravenous injection of endotoxin (10 micrograms/kg) 10 min after administration of anti-TNF alpha antibody (Antibody Group) or same volume of control rabbit serum (Control Group). PAI activity was measured by Coatest PAI, and PAI-1 mRNA was measured semi-quantitatively by high-performance liquid chromatography after reverse transcription and polymerase chain reaction. Increases in PAI activity 4 h after endotoxin treatment were significantly smaller in the Antibody Group than in the Control Group, while increases in PAI-1 mRNA were significantly smaller at 2 h in the Antibody Group. These results suggest that TNF alpha is responsible, at least in part, for the induction of PAI-1 by endotoxin in vivo.
authors.affiliation: Department of Emergency Medicine, University of Tsukuba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
authors.forename: M
authors.initials: M
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004731:Endotoxins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha