title: Induction of anaphylatoxin C5a receptors in rat hepatocytes by lipopolysaccharide in vivo: mediation by interleukin-6 from Kupffer cells.
abstract: OBJECTIVE
  In normal rat liver, anaphylatoxin C5a induces glucose output from hepatocytes indirectly via prostanoids released from Kupffer cells. Correspondingly, it was found that hepatocytes, in contrast to Kupffer cells, did not express C5a receptors. Lipopolysaccharide (LPS) has been reported to enhance C5a receptor expression in murine livers. This might be the result of de novo expression in hepatocytes.
  
  
  METHODS
  C5a receptor expression was investigated in hepatocytes after in vivo treatment of rats with LPS and in vitro stimulation of isolated cells with LPS and proinflammatory cytokines on messenger RNA (mRNA) and protein level, and functionally in isolated hepatocytes and perfused liver.
  
  
  RESULTS
  In vivo treatment of rats with LPS induced C5a receptor mRNA and protein in hepatocytes with a maximum after 8-10 hours. At this time-point, C5a directly activated glycogen phosphorylase in isolated hepatocytes and enhanced glucose output in perfused livers without the involvement of prostanoids. LPS failed to induce C5a receptors in cultured hepatocytes in vitro, whereas interleukin (IL) 6 and IL-1beta, which are known to be released from Kupffer cells on stimulation with LPS, did so. In cocultures of hepatocytes with Kupffer cells, LPS induced C5a receptors in hepatocytes in an IL-6-dependent manner.
  
  
  CONCLUSIONS
  Thus, IL-6 from Kupffer cells appears to be the main mediator of LPS-induced de novo expression of C5a receptors in hepatocytes.
authors.affiliation: Institut für Biochemie und Molekulare Zellbiologie, Georg-August-Universität Göttingen, Germany.
authors.forename: Milena
authors.initials: M
authors.lastname: Koleva
authors.forename: Gerald
authors.initials: G
authors.lastname: Schlaf
authors.forename: Regine
authors.initials: R
authors.lastname: Landmann
authors.forename: Otto
authors.initials: O
authors.lastname: Götze
authors.forename: Kurt
authors.initials: K
authors.lastname: Jungermann
authors.forename: Henrike L
authors.initials: HL
authors.lastname: Schieferdecker
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019446:Endotoxemia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D005947:Glucose / Q000378:metabolism; D024981:Glycogen Phosphorylase / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D007728:Kupffer Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D010648:Phenylacetates / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement / Q000235:genetics*; D013449:Sulfonamides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D016861:Cyclooxygenase Inhibitors; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D010648:Phenylacetates; D012333:RNA, Messenger; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D024981:Glycogen Phosphorylase; D005947:Glucose; C051762:daltroban; D007213:Indomethacin