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

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

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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)
Pages (from-to)G991-G1001
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume282
Issue number6 45-6
StatePublished - Jun 27 2002
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Keywords

  • Cytokines
  • Hepatocellular cholestasis
  • Macrophages
  • Obstructive cholestasis

Cite this

González, H. E., Eugenín, E. A., Garcés, G., Solís, N., Pizarro, M., Accatino, L., & Sáez, J. C. (2002). Regulation of hepatic connexins in cholestasis: Possible involvement of Kupffer cells and inflammatory mediators. American Journal of Physiology - Gastrointestinal and Liver Physiology, 282(6 45-6), G991-G1001.