Original CommunicationsTumor necrosis factor-α and interleukin-6 reduce bile canalicular contractions of rat hepatocytes*,**,*
Section snippets
Chemicals
Recombinant rat TNF-α (specific activity > 2 × 107 U/mg; endotoxin < 0.1 ng/μg) and recombinant rat IL-6 (specific activity > 1 × 108 U/μg; endotoxin < 0.1 ng/μg) were purchased from Pepro Tech EC, Ltd (London, United Kingdom). These cytokines were dissolved in phosphate-buffered saline containing 0.1% bovine serum albumin (Intergen Co, Purchase, NY). Other agents were purchased as follows: fetal bovine serum (ICN Biochemicals, Inc, Aurora, Ohio); L-15 medium and gentamicin (Gibco Laboratories,
Effects of TNF-α and IL-6 on BC contraction
Animated time-lapse images showed repeated BC contractions and enlargement between hepatocyte couplets several times within 2 hours (Fig 2).Fig 2, A and D show the maximal BC enlargement and the closed BC, respectively. In most cases BC gradually expanded and suddenly contracted. The time
Discussion
In the current study we showed that administration of TNF-α or IL-6 to rats could result in a decrease of bile excretion and in an increase of total bile acid in serum. There are 3 possible reasons why the amount of the bile was reduced without mechanical obstruction of the biliary tree: (1) prehepatic, (2) intrahepatic, and (3) posthepatic impairment. The prehepatic cause of cholestasis is overabundance of bilirubin, which is induced by blood transfusion.3 Hemolysis of transfused red blood
Acknowledgements
We thank Mr H. Araake, Ms M. Kuwano, and Ms Y. Tanaka-Takahashi for technical assistance. We are also grateful to Dr Tomoko Sonoda (Department of Public Health, Sapporo Medical University) for her suggestions about statistics and to Mr K. Barrymore for help with the article.
References (26)
- et al.
Jaundice due to bacterial infection
Gastroenterology
(1979) - et al.
Jaundice in severe bacterial infection
Gastroenterology
(1976) - et al.
Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis
Hepatology
(1995) - et al.
Regulation of hepatocyte bile salt transporters by endotoxin and inflammatory cytokines in rodents
Gastroenterology
(1996) - et al.
The rat canalicular conjugate export pump (Mrp2) is down-regulated in intrahepatic and obstructive cholestasis
Gastroenterology
(1997) - et al.
Hepatocyte transport of bile acids and organic anions in endotoxemic rats: impaired uptake and secretion
Gastroenterology
(1997) Preparation of isolated rat liver cells
Methods Cell Biol
(1976)- et al.
Hepatocyte tight-junctional permeability is increased in rat experimental colitis
Gastroenterology
(1997) - et al.
Localization of the 7H6 antigen at tight junctions correlates with the paracellular barrier function of MDCK cells
Exp Cell Res
(1994) - et al.
Effect of tumor necrosis factor alpha on intrahepatic bile duct epithelial cell of rat liver
Hepatology
(1996)
Postoperative hyperbilirubinemia after resection of thoracic esophageal cancer
Am J Gastroenterol
Inflammation-induced cholestasis
J Gastroenterol Hepatol
Noticeable hyperbilirubinemia following major hepatectomy in patients with biliary tract carcinoma
Nippon Geka Hokan
Cited by (10)
TGF-β-SMAD3 signaling mediates hepatic bile acid and phospholipid metabolism following lithocholic acid-induced liver injury
2012, Journal of Lipid ResearchLiver involvement in children with Familial Mediterranean fever
2012, Digestive and Liver DiseaseCitation Excerpt :Changes in liver function tests during the acute FMF attacks have been studied in an adult patient group, and found that 27% had hyperbilirubinemia and 10% had elevated liver enzymes during acute attack of FMF [14]. Cytokine stimulation during acute attacks of FMF may cause to decrease in the bile excretion and activity of UDP-glucuronosyltransferase, and may also increase the permeability of tight junctions in intrahepatic bile duct-derived epithelial cells [15]. As a result increased cytokine stimulation may lead to hyperbilirubinemia during the acute attacks of FMF.
Sepsis and cholestasis
2004, Clinics in Liver DiseaseNon-amyloid liver involvement in familial Mediterranean fever: A systematic literature review
2020, Liver International
- *
Supported in part by Grants-in-Aid from the Ministry of Education, Science, Sports and Culture, Japan (09470256 and 12470265 for K. Hirata, 12670211 for T. Mitaka, and 1247243 for Y. Mochizuki) and by a Grant-in-Aid from the Sapporo Medical University Foundation for Promotion of Medical Science (for S. Ikeda).
- **
Reprint requests: Toshihiro Mitaka, MD, PhD, Department of Pathology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-ku, S-1, W-17, Sapporo 060-8556, Japan.
- *
0039-6060/2003/$30.00 + 0