Bile ducts and portal and central veins are major producers of tumor necrosis factor alpha in regenerating rat liver.


Journal Article

BACKGROUND & AIMS: Tumor necrosis factor (TNF) alpha mediates both liver injury and regeneration. Kupffer cells are thought to produce TNF because gadolinium chloride (GdCl), a drug that depletes Kupffer cells, prevents TNF-mediated injury. However, GdCl increases liver TNF and regeneration after partial hepatectomy (PH), suggesting that other cells produce TNF during regeneration. The aim of this study was to identify the source(s) of TNF after PH in normal and Kupffer cell-depleted rats. METHODS: Livers were harvested at 0, 1, or 48 hours after PH from saline- or GdCl-treated rats. TNF expression was evaluated by in situ reverse-transcription polymerase chain reaction and immunohistochemistry. RESULTS: In saline-treated rats, neither TNF transcripts nor protein was detected before PH, but both increased after PH. One hour after PH, 64% +/- 8% portal areas had TNF-positive bile ducts or veins and 61% +/- 1% central veins were TNF positive; by 48 hours, 57% +/- 1% portal areas, 40% +/- 1% central veins, and a few sinsusoidal cells expressed TNF. In GdCl-treated rats, TNF was expressed in 22% +/- 6% portal areas before PH; in 76% +/- 3% portal areas and 75% central veins at 1 hour; and in 88% +/- 2% portal areas and 80% +/- 9% central veins at 48 hours after PH. CONCLUSIONS: In the regenerating livers of both normal and Kupffer cell-depleted rats, bile ducts and veins are the predominant sources of TNF-alpha.

Full Text

Duke Authors

Cited Authors

  • Loffreda, S; Rai, R; Yang, SQ; Lin, HZ; Diehl, AM

Published Date

  • June 1997

Published In

Volume / Issue

  • 112 / 6

Start / End Page

  • 2089 - 2098

PubMed ID

  • 9178702

Pubmed Central ID

  • 9178702

International Standard Serial Number (ISSN)

  • 0016-5085

Digital Object Identifier (DOI)

  • 10.1053/gast.1997.v112.pm9178702


  • eng

Conference Location

  • United States