IL-1beta mediates induction of hepatic type 1 plasminogen activator inhibitor in response to local tissue injury.
Type 1 plasminogen activator inhibitor (PAI-1), a major physiological inhibitor of plasminogen activation, is an important component of the hepatic acute phase response. We studied the acute phase regulation of murine hepatic PAI-1 in response to systemic toxicity and local tissue injury in both wild-type mice and in mice in which the interleukin (IL)-1beta gene had been inactivated by gene targeting. Endotoxin induced plasma PAI-1 antigen levels and PAI-1 mRNA accumulation in liver to the same extent in both wild-type and IL-1beta-deficient mice. In contrast, turpentine increased plasma PAI-1 and hepatic PAI-1 mRNA accumulation in wild-type mice but not in IL-1beta-deficient mice. Intraperitoneal injection of murine IL-1beta rapidly increased plasma PAI-1 and hepatic PAI-1 mRNA in both wild-type and IL-1beta-deficient mice. These results suggest that IL-1beta is a critical inducer of hepatic PAI-1 gene expression during the acute phase response to local tissue injury. In situ hybridization studies revealed that hepatocytes are the cells primarily responsible for the hepatic expression of the PAI-1 gene induced by lipopolysaccharide and turpentine.
Seki
T
T
Department of Nutrition, Nihon University College of Bioresource Sciences, Tokyo 154-8516, Japan.
Healy
A M
AM
Fletcher
D S
DS
Noguchi
T
T
Gelehrter
T D
TD
D000210:Acute-Phase Reaction / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000032:analysis; D004731:Endotoxins / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007509:Irritants / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014425:Turpentine / Q000494:pharmacology; D014947:Wounds and Injuries / Q000378:metabolism*
D000941:Antigens; D004731:Endotoxins; D007375:Interleukin-1; D007509:Irritants; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014425:Turpentine