title: Cellular fibronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury.
abstract: OBJECTIVE
  To examine the consequences of cellular fibronectin (cFn) accumulation during alcohol-induced injury, and investigate whether increased cFn could have an effect on hepatocytes (HCs) by producing factors that could contribute to alcohol-induced liver injury.
  
  
  METHODS
  HCs were isolated from rats fed a control or ethanol liquid diet for four to six weeks. Exogenous cFn (up to 7.5 μg/mL) was added to cells cultured for 20 h, and viability (lactate dehydrogenase,LDH), apoptosis (caspase activity) and secretion of proinflammatory cytokines (tumor necrosis factor alpha, TNF-α and interleukin 6 IL-6), matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) was determined. Degradation of iodinated cFn was determined over a 3 h time period in the preparations.
  
  
  RESULTS
  cFn degradation is impaired in HCs isolated from ethanol-fed animals, leading to its accumulation in the matrix. Addition of exogenous cFn did not affect viability of HCs from control or ethanol-fed animals, and apoptosis was affected only at the higher concentration. Secretion of MMPs, TIMPs, TNF-α and IL-6, however, was increased by exogenously added cFn, with HCs from ethanol-fed animals showing increased susceptibility compared to the controls.
  
  
  CONCLUSIONS
  These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage.
authors.affiliation: Razia S Aziz-Seible, Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, United States.
authors.forename: Razia S
authors.initials: RS
authors.lastname: Aziz-Seible
authors.forename: Benita L
authors.initials: BL
authors.lastname: McVicker
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.forename: Carol A
authors.initials: CA
authors.lastname: Casey