title: Interleukin 6 upregulates TNF-alpha-dependent C3-stimulating activity through enhancement of TNF-alpha specific binding on rat liver epithelial cells.
abstract: The authors investigated the role of tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), two major pro-inflammatory cytokines, in the stimulation of the third component of complement (C3) production by rat liver epithelial cells. Though often considered as the most potent inflammatory cytokine, IL-6 alone displayed no activity, whereas TNF-alpha upregulated C3 production in a dose-dependent manner. However, IL-6 was shown to synergistically stimulate C3 production in the presence of TNF-alpha. To account for this interaction, it was postulated that IL-6 modulates the binding of TNF-alpha on liver target cells. That IL-6 increased the binding of TNF-alpha on the surface of the hepatic cells, whereas TNF-alpha alone downregulated its own specific binding capacity is reported. Furthermore, this upregulatory effect of IL-6 was mainly attributable to an increase in the number of plasma membrane TNF-alpha specific receptors, with little change in their affinity. These results suggest that the synergistic IL-6 activity on C3 production may occur, at least partially, through its capacity to upregulate the number of TNF-alpha receptors on the surface of the rat liver epithelial cells.
authors.affiliation: Laboratoire de Biochimie Médicale, Hôpital d'Enfants, Dijon, France.
authors.forename: D
authors.initials: D
authors.lastname: Platel
authors.forename: A
authors.initials: A
authors.lastname: Bernard
authors.forename: G
authors.initials: G
authors.lastname: Mack
authors.forename: M
authors.initials: M
authors.lastname: Guiguet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003176:Complement C3 / Q000276:immunology*; D004847:Epithelial Cells; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D008099:Liver / Q000166:cytology; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D003176:Complement C3; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha