Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats.
Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl) should inhibit liver regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated and control rats. Functional assays and Northern blot analysis of a Kupffer cell-specific mRNA confirmed that GdCl depleted Kupffer cells. Despite this, semiquantitative reverse transcription-polymerase chain reaction analysis of total hepatic RNA showed six- to eightfold higher levels of TNF transcripts in GdCl-treated rats. In this group, PH caused 12-to 16-fold greater induction of interleukin-6, a TNF-inducible cytokine, and two- to threefold greater induction of several cytokine-regulated genes (c-jun, C/EBP-beta, and C/EBP-delta). GdCl also amplified regeneration-associated increases in the DNA binding activity of AP-1, a growth regulatory transcription factor. Furthermore, hepatic incorporation of [3H]thymidine, expression of the S-phase antigen, proliferating cell nuclear antigen, and the hepatocyte mitotic index were each significantly greater in GdCl-treated rats. Thus, although GdCl causes Kupffer cell depletion, it does not decrease liver TNF and actually enhances liver regeneration after PH.
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Related Subject Headings
- Tumor Necrosis Factor-alpha
- Transcription Factors
- Rats, Sprague-Dawley
- Rats
- RNA, Messenger
- Proliferating Cell Nuclear Antigen
- Oligonucleotide Probes
- Molecular Sequence Data
- Male
- Liver Regeneration
Citation
Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Tumor Necrosis Factor-alpha
- Transcription Factors
- Rats, Sprague-Dawley
- Rats
- RNA, Messenger
- Proliferating Cell Nuclear Antigen
- Oligonucleotide Probes
- Molecular Sequence Data
- Male
- Liver Regeneration