Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators

González HE; Eugenin, EA; Garces, G; Solís N.; Pizarro M.; Accatino L.; Sáez JC

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-? and interleukins-1? 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.

Más información

Título según WOS: Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators
Título según SCOPUS: Regulation of hepatic connexins in cholestasis: Possible involvement of Kupffer cells and inflammatory mediators
Título de la Revista: AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volumen: 282
Número: 6
Editorial: AMER PHYSIOLOGICAL SOC
Fecha de publicación: 2002
Página de inicio: G991
Página final: G1001
Idioma: English
DOI:

10.1152/ajpgi.00298.2001

Notas: ISI, SCOPUS