title: Bile ducts and portal and central veins are major producers of tumor necrosis factor alpha in regenerating rat liver.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, The Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: S
authors.initials: S
authors.lastname: Loffreda
authors.forename: R
authors.initials: R
authors.lastname: Rai
authors.forename: S Q
authors.initials: SQ
authors.lastname: Yang
authors.forename: H Z
authors.initials: HZ
authors.lastname: Lin
authors.forename: A M
authors.initials: AM
authors.lastname: Diehl
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000378:metabolism*; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism*; D008297:Male; D011169:Portal Vein / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D014409:Tumor Necrosis Factor-alpha