title: Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators.
abstract: Hepatocyte gap junction proteins, connexins (Cxs) 26 and 32, are downregulated during obstructive cholestasis (OC) and lipopolysaccharide hepatocellular cholestasis (LPS-HC). We investigated rat hepatic Cxs during ethynylestradiol hepatocellular cholestasis (EE-HC) and choledochocaval fistula (CCF) and compared them with OC and LPS-HC. Levels (immunoblotting) and cellular distribution (immunofluorescence) of Cx26, -32, and -43, as well as macrophage infiltration, were studied in livers of rats under each condition. Cx26 and -32 were reduced in LPS-HC, OC, and CCF. However, in EE-HC, Cx26 did not change and Cx32 was increased. Prominent inflammation occurred in LPS-HC, OC, and CCF, which was associated with increased levels of Cx43 in LPS-HC and OC but not CCF. No inflammation nor changes in Cx43 levels occurred during EE-HC. In cultured hepatocytes, dye coupling was reduced by tumor necrosis factor-alpha and interleukins-1beta and -6, whereas reduction induced by LPS required coculture with Kupffer cells. Thus hepatocyte gap junctions are downregulated in forms of cholestasis associated with inflammation, and reduced intercellular communication might be induced in part by proinflammatory mediators.
authors.affiliation: Departamento de Ciencias Fisiológicas, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Hernán E
authors.initials: HE
authors.lastname: González
authors.forename: Eliseo A
authors.initials: EA
authors.lastname: Eugenín
authors.forename: Gladys
authors.initials: G
authors.lastname: Garcés
authors.forename: Nancy
authors.initials: N
authors.lastname: Solís
authors.forename: Margarita
authors.initials: M
authors.lastname: Pizarro
authors.forename: Luigi
authors.initials: L
authors.lastname: Accatino
authors.forename: Juan C
authors.initials: JC
authors.lastname: Sáez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001658:Biliary Fistula / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002779:Cholestasis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007728:Kupffer Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000097002:Gap Junction beta-1 Protein
chemical_list: D000970:Antineoplastic Agents; D000072259:Connexin 26; D017630:Connexins; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000097002:Gap Junction beta-1 Protein; C000607044:Gjb2 protein, rat