title: Immunohistochemical distribution of activated nuclear factor kappaB and peroxisome proliferator-activated receptors in carbon tetrachloride-induced chronic liver injury in rats.
abstract: We investigated the immunohistochemical distribution of active NF-kappaB p65 and peroxisome proliferator-activated receptor (PPAR) subtypes alpha and gamma in the different phases of liver steatonecrosis and cirrhosis induced in rats after 3 and 9 weeks of carbon tetrachloride (CCl4) intoxication. CCl4 treatment can induce changes in the expression of NF-kappaB and PPARs. Immunohistochemical analysis of liver tissue sections from rats with steatonecrosis or cirrhosis demonstrated a significant increase in the number of NF-kappaB-positive and TNF-alpha-positive hepatocytes and Kupffer cells. In healthy controls, no expression of active NF-kappaB was detected. In previous studies, we have demonstrated that Kupffer cells isolated from rats with CCl4-induced steatonecrosis produced more reactive oxygen intermediates than cells isolated from normal rats. These oxidants could activate NF-kappaB and lead to an overexpression of TNF-alpha, observed in liver tissue sections. After CCl4 ingestion, the rat livers demonstrated a significantly decreased number of hepatocytes expressing PPARalpha and PPARgamma and a significantly increased number of ED2-positive Kupffer cells expressing these transcription factors, compared to normal. The activation of the p65 isoform of NF-kappaB correlates negatively with transcription of the alpha and gamma isoforms of PPAR in hepatocytes, and positively in Kupffer cells. These results suggest that the regulation and the role of these two transcription factors differ in the two cell types studied.
authors.affiliation: EA 2405, IFR 31, BP 84225, 31432, Toulouse Cedex 4, France. orfila@toulouse.inserm.fr
authors.forename: Claudine
authors.initials: C
authors.lastname: Orfila
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lepert
authors.forename: Laurent
authors.initials: L
authors.lastname: Alric
authors.forename: Georges
authors.initials: G
authors.lastname: Carrera
authors.forename: Maryse
authors.initials: M
authors.lastname: Béraud
authors.forename: Bernard
authors.initials: B
authors.lastname: Pipy
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000008:administration & dosage / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury; D002908:Chronic Disease; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007728:Kupffer Cells / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000032:analysis*; D047493:PPAR alpha / Q000032:analysis; D047495:PPAR gamma / Q000032:analysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D016328:NF-kappa B; D047493:PPAR alpha; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D014409:Tumor Necrosis Factor-alpha; D002251:Carbon Tetrachloride