Interleukin-6 inhibits hepatocyte taurocholate uptake and sodium- potassium-adenosinetriphosphatase activity

R. M. Green*, J. F. Whiting, A. B. Rosenbluth, D. Beier, J. L. Gollan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The potential effects of cytokines on hepatocellular transport functions remain undefined. Interleukin-6 (IL-6) is a cytokine that is produced in sepsis, hepatitis, and other inflammatory conditions often associated with cholestasis. Using cultured rat hepatocytes, we have investigated the effects of IL-6 on hepatocellular bile salt uptake. Because hepatocyte Na+-K+- adenosinetriphosphatase (ATPase) produces the electrochemical gradient that drives sodium-dependent bile salt cotransport, we also examined the effects of IL-6 on Na+-K+-ATPase activity. Hepatocytes cultured for 20 h in media containing IL-6 exhibited a dose-dependent noncompetitive inhibition of [3H]taurocholate uptake, which was maximal at an IL-6 dose of 100 U/ml. IL- 6 treatment had no effect on hepatocyte sodium-independent taurocholate uptake. Northern blotting of RNA from cultured hepatocytes revealed that IL- 6 had no effect on steady-state RNA levels of the Na+-taurocholate transporter (Ntcp). Hepatocytes incubated with IL-6 for 20 h, however, exhibited a 55% decrease in hepatocyte Na+-K+-ATPase activity. This effect also was dose dependent, with maximal inhibition occurring at an IL-6 dose of 100 U/ml. Similar treatment with IL-6 did not influence hepatocyte Mg2+- ATPase activity. The inhibition of Na+-K+-ATPase activity induced by IL-6 provides a putative mechanism for the observed inhibition of sodium-dependent taurocholate uptake. Since modulation of bile salt transport and Na+-K+- ATPase activity occurred at IL-6 concentrations comparable to the serum levels observed in patients with severe inflammatory states, these findings have potential pathophysiological relevance for the cholestasis of sepsis and other inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)G1094-G1100
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume267
Issue number6 30-6
DOIs
StatePublished - Dec 1 1994

Keywords

  • bile salts
  • cytokines
  • transport

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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