Tumor necrosis factor–alpha decreases hepatocyte bile salt uptake and mediates endotoxin‐induced cholestasis

Tumor necrosis factor–alpha decreases hepatocyte bile salt uptake and mediates... Tumor necrosis factor–alpha (TNF,α), a cytokine that is produced in a variety of inflammatory diseases associated with cholestasis, is believed to be the primary mediator of the systemic effects of endotoxin. Thus, we have investigated the role of TNFα in the pathogenesis of endotoxin‐induced cholestasis in intact animals, and in the uptake of taurocholate by cultured hepatocytes. Male Sprague‐Dawley rats received either intravenous (IV) endotoxin (7.5 mg/kg) or monoclonal anti‐TNFα antibody followed by endotoxin. Basal bile flow and bile salt excretion were measured for a 2‐hour period, after which all animals received an IV bolus of taurocholate (10 μmol/100 g body weight). Endotoxin decreased basal bile flow by 41% and bile salt stimulated bile flow by 38% (n = 12; P < .01). Basal bile salt excretion was decreased 86% after endotoxin administration. Passive immunization with anti‐TNFα antibody blocked this endotoxin‐associated cholestasis. In addition, rat hepatocytes were isolated and cultured in the presence of either endotoxin (10 μg/mL) or TNFα (100 ng/mL) for 24 hours. These primary hepatocyte cultures exhibited a dose‐ and timedependent, noncompetitive, inhibition of taurocholate uptake. We postulate that TNFα is an important mediator of the cholestasis of sepsis. (HEPATOLOGY 1995; 22:1273–1278.). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Hepatology Wiley

Tumor necrosis factor–alpha decreases hepatocyte bile salt uptake and mediates endotoxin‐induced cholestasis

Loading next page...
 
/lp/wiley/tumor-necrosis-factor-alpha-decreases-hepatocyte-bile-salt-uptake-and-J9rdeMQBpF
Publisher
Wiley
Copyright
Copyright © 1995 American Association for the Study of Liver Diseases
ISSN
0270-9139
eISSN
1527-3350
DOI
10.1002/hep.1840220437
Publisher site
See Article on Publisher Site

Abstract

Tumor necrosis factor–alpha (TNF,α), a cytokine that is produced in a variety of inflammatory diseases associated with cholestasis, is believed to be the primary mediator of the systemic effects of endotoxin. Thus, we have investigated the role of TNFα in the pathogenesis of endotoxin‐induced cholestasis in intact animals, and in the uptake of taurocholate by cultured hepatocytes. Male Sprague‐Dawley rats received either intravenous (IV) endotoxin (7.5 mg/kg) or monoclonal anti‐TNFα antibody followed by endotoxin. Basal bile flow and bile salt excretion were measured for a 2‐hour period, after which all animals received an IV bolus of taurocholate (10 μmol/100 g body weight). Endotoxin decreased basal bile flow by 41% and bile salt stimulated bile flow by 38% (n = 12; P < .01). Basal bile salt excretion was decreased 86% after endotoxin administration. Passive immunization with anti‐TNFα antibody blocked this endotoxin‐associated cholestasis. In addition, rat hepatocytes were isolated and cultured in the presence of either endotoxin (10 μg/mL) or TNFα (100 ng/mL) for 24 hours. These primary hepatocyte cultures exhibited a dose‐ and timedependent, noncompetitive, inhibition of taurocholate uptake. We postulate that TNFα is an important mediator of the cholestasis of sepsis. (HEPATOLOGY 1995; 22:1273–1278.).

Journal

HepatologyWiley

Published: Oct 1, 1995

References

  • Effect of different sepsis‐related cytokines on lipid synthesis by isolated hepatocytes
    Vara, Vara; Arias‐Diaz, Arias‐Diaz; Torres‐Melero, Torres‐Melero; Garcia, Garcia; Rodriguez, Rodriguez; Balibrea, Balibrea
  • Interleukin‐6 inhibits hepatocyte taurocholate uptake and sodium‐potassium‐adenosinetriphosphatase activity
    Green, Green; Whiting, Whiting; Rosenbluth, Rosenbluth; Beier, Beier; Gollan, Gollan
  • Endotoxin levels measured by chromogenic assay in portal, hepatic, and peripheral venous blood in patients with cirrhosis
    Lumsden, Lumsden; Henderson, Henderson; Kuner, Kuner
  • Alterations of bile acid and bumetanide uptake during culturing of rat hepatocytes
    Follman, Follman; Petzinger, Petzinger; Kinne, Kinne
  • Comparison of uptake kinetics in freshly isolated suspensions and short‐term primary cultures of rat hepatocytes
    Kukongviriyapan, Kukongviriyapan; Stacey, Stacey

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off