Regulation of hepatic connexins in cholestasis

Possible involvement of Kupffer cells and inflammatory mediators

Hernán E. González, Eliseo Eugenin, Gladys Garcés, Nancy Solís, Margarita Pizarro, Luigi Accatino, Juan C. Sáez

Research output: Contribution to journalArticle

58 Citations (Scopus)

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-α and interleukins-1β 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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume282
Issue number6 45-6
StatePublished - Jun 27 2002
Externally publishedYes

Fingerprint

Connexins
Kupffer Cells
Cholestasis
Liver
Lipopolysaccharides
Fistula
Hepatocytes
Connexin 43
Inflammation
Down-Regulation
Gap Junctions
Coculture Techniques
Interleukin-1
Immunoblotting
Fluorescent Antibody Technique

Keywords

  • Cytokines
  • Hepatocellular cholestasis
  • Macrophages
  • Obstructive cholestasis

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Regulation of hepatic connexins in cholestasis : Possible involvement of Kupffer cells and inflammatory mediators. / González, Hernán E.; Eugenin, Eliseo; Garcés, Gladys; Solís, Nancy; Pizarro, Margarita; Accatino, Luigi; Sáez, Juan C.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 282, No. 6 45-6, 27.06.2002.

Research output: Contribution to journalArticle

González, Hernán E. ; Eugenin, Eliseo ; Garcés, Gladys ; Solís, Nancy ; Pizarro, Margarita ; Accatino, Luigi ; Sáez, Juan C. / Regulation of hepatic connexins in cholestasis : Possible involvement of Kupffer cells and inflammatory mediators. In: American Journal of Physiology - Gastrointestinal and Liver Physiology. 2002 ; Vol. 282, No. 6 45-6.
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