OBJECTIVE: To assess the effects of sex steroids on hepatic inflammatory pathways in short-term chronically ethanol-fed rats. METHODS: Ovariectomized female Wistar rats (8-12 weeks old, n = 8 per treatment group) were implanted with osmotic pumps releasing 17β-estradiol (20 μg/24 h) or testosterone (25 μg/24 h) and fed liquid diets with or without ethanol (8 % w/v) for two weeks. Hepatic expression of IκBα/β, TNF-α, and IL-6 mRNA was examined by real-time PCR. Liver (nuclear) NFκB, IκBα and β, IL-6, and IL-6Rα protein expression was examined by enzyme-linked immunosorbent assay (ELISA) or Western blot. RESULTS: Estrogen alone induced greater steatosis, NFκB translocation, TNF-α mRNA, as well as IL-6, and IL-6R protein. Alcohol consumption along with estrogen treatment further increased steatosis, NFκB translocation, TNF-α mRNA, and IL-6 protein. Conversely, neither estrogen nor ethanol consumption induced IκBα or IκBβ mRNA or protein expression, while testosterone robustly induced these inhibitory proteins regardless of treatment. CONCLUSIONS: Estrogen exposure enhances alcohol-induced liver inflammation, and the anti-inflammatory effects of testosterone in the liver might be related to induction of IκB. Elevated inflammation in response to estrogen may overwhelm the regenerative influence of IL-6 in liver, leading to increased steatosis and greater liver damage.
OBJECTIVE: To assess the effects of sex steroids on hepatic inflammatory pathways in short-term chronically ethanol-fed rats. METHODS: Ovariectomized female Wistar rats (8-12 weeks old, n = 8 per treatment group) were implanted with osmotic pumps releasing 17β-estradiol (20 μg/24 h) or testosterone (25 μg/24 h) and fed liquid diets with or without ethanol (8 % w/v) for two weeks. Hepatic expression of IκBα/β, TNF-α, and IL-6 mRNA was examined by real-time PCR. Liver (nuclear) NFκB, IκBα and β, IL-6, and IL-6Rα protein expression was examined by enzyme-linked immunosorbent assay (ELISA) or Western blot. RESULTS: Estrogen alone induced greater steatosis, NFκB translocation, TNF-α mRNA, as well as IL-6, and IL-6R protein. Alcohol consumption along with estrogen treatment further increased steatosis, NFκB translocation, TNF-α mRNA, and IL-6 protein. Conversely, neither estrogen nor ethanol consumption induced IκBα or IκBβ mRNA or protein expression, while testosterone robustly induced these inhibitory proteins regardless of treatment. CONCLUSIONS: Estrogen exposure enhances alcohol-induced liver inflammation, and the anti-inflammatory effects of testosterone in the liver might be related to induction of IκB. Elevated inflammation in response to estrogen may overwhelm the regenerative influence of IL-6 in liver, leading to increased steatosis and greater liver damage.
Authors: G L Su; R D Klein; A Aminlari; H Y Zhang; L Steinstraesser; W H Alarcon; D G Remick; S C Wang Journal: Hepatology Date: 2000-04 Impact factor: 17.425
Authors: C J Grossman; M Nienaber; C L Mendenhall; P Hurtubise; G A Roselle; S Rouster; N Weber; G Schmitt; P S Gartside Journal: Alcohol Clin Exp Res Date: 1993-08 Impact factor: 3.455
Authors: F Y Lee; R H Lu; Y T Tsai; H C Lin; M C Hou; C P Li; T M Liao; L F Lin; S S Wang; S D Lee Journal: Scand J Gastroenterol Date: 1996-05 Impact factor: 2.423
Authors: Chandrashekhar D Kamat; Jessica E Thorpe; Satyendra S Shenoy; Antonio Ceriello; Dixy E Green; Linda A Warnke; Michael A Ihnat Journal: BMC Cardiovasc Disord Date: 2007-01-18 Impact factor: 2.298