title: Endotoxin- and cytokine-mediated effects on liver cell proliferation and lipid metabolism after partial hepatectomy: a study with recombinant N-terminal bactericidal/permeability-increasing protein and interleukin-1 receptor antagonist.
abstract: This study was performed to clarify the mechanisms underlying post-resection changes in liver cell proliferation and metabolism. To assess the role of gut-derived endotoxaemia and endogenous cytokines in these changes, the effects of peri-operative treatment with either the lipopolysaccharide-neutralizing bactericidal/permeability-increasing protein or interleukin-1 receptor antagonist were investigated at 24 h after two-thirds hepatectomy in rats. Peri-operative treatment with either agent caused enhanced expression of proliferating cell nuclear antigen (PCNA) and reduced lipid accumulation. Activity of the hexose monophosphate shunt was significantly decreased after partial hepatectomy and restored by interleukin-1 receptor antagonist only. After partial hepatectomy, bile canalicular alkaline phosphatase activity was significantly increased in pericentral zones and redistributed to both bile canalicular and sinusoidal membranes of hepatocytes. These effects were not significantly influenced by either treatment. It is concluded that endotoxin restricts liver cell proliferation and leads to lipid accumulation following partial hepatectomy, and that interleukin-1 is a principal mediator in these processes. Furthermore, interleukin-1 mediates a repression of the pentose phosphate pathway. These changes may be of significance with respect to liver function, at least in the early phase after partial hepatectomy.
authors.affiliation: Department of Cell Biology and Histology, University of Amsterdam, Netherlands.
authors.forename: I H
authors.initials: IH
authors.lastname: Straatsburg
authors.forename: M A
authors.initials: MA
authors.lastname: Boermeester
authors.forename: A P
authors.initials: AP
authors.lastname: Houdijk
authors.forename: W M
authors.initials: WM
authors.lastname: Frederiks
authors.forename: R I
authors.initials: RI
authors.lastname: Wesdorp
authors.forename: P A
authors.initials: PA
authors.lastname: Van Leeuwen
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Noorden
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004731:Endotoxins / Q000502:physiology*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006498:Hepatectomy; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000502:physiology*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D008565:Membrane Proteins; D011994:Recombinant Proteins; D012795:Sialoglycoproteins; C021623:bactericidal permeability increasing protein; D010734:Phosphogluconate Dehydrogenase; D000469:Alkaline Phosphatase; D005952:Glucose-6-Phosphatase