Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in choledocho-venous fistula rats

Enrico Souto, Hideyuki Miyoshi, Raymond N. Dubois, Gregory J. Gores

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We have previously demonstrated that after bile duct ligation hepatocytes express Bcl-2, although the mechanisms regulating Bcl-2 expression were not identified. Our aim was to determine if biliary constituents induce hepatocellular expression of Bcl-2 by a cyclooxygenase-2 (COX-2)-dependent mechanism. We used the choledocho-venous fistula (CVF) rat model for these studies and inhibited COX-2 by feeding the animals nimesulide, a selective inhibitor of COX-2 activity. Serum bile acids were 70-fold greater in CVF animals compared with controls, although liver histology and serum alanine aminotransferase values remained normal for the duration of the study. Neither Bcl-2 nor COX-2 was detected in sham-operated animals. However, Bcl-2 was expressed in hepatocytes but not in other liver cells in the CVF animals. In contrast, COX-2 protein was identified in Kupffer cells but not in hepatocytes of CVF animals. Hepatic Bcl-2 protein expression was four-fold lower in the livers from nimesulide-treated CVF rats. In conclusion, high circulating concentrations of biliary constituents are associated with stimulation of de novo hepatocyte expression of Bcl-2 and Kupffer cell expression of COX-2. These data suggest Kupffer cell-derived prostanoids may regulate Bcl-2 expression in the hepatocyte.

Original languageEnglish
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume280
Issue number5 43-5
StatePublished - May 1 2001
Externally publishedYes

Fingerprint

Kupffer Cells
Cyclooxygenase 2
Fistula
Hepatocytes
nimesulide
Liver
Cyclooxygenase 2 Inhibitors
Bile Ducts
Bile Acids and Salts
Serum
Alanine Transaminase
Prostaglandins
Ligation
Histology
Reference Values
Proteins

Keywords

  • Bile acids
  • Nimesulide
  • Prostanoids

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology
  • Physiology (medical)

Cite this

Kupffer cell-derived cyclooxygenase-2 regulates hepatocyte Bcl-2 expression in choledocho-venous fistula rats. / Souto, Enrico; Miyoshi, Hideyuki; Dubois, Raymond N.; Gores, Gregory J.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 280, No. 5 43-5, 01.05.2001.

Research output: Contribution to journalArticle

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