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AIM:To examine the consequences of cellular f ibronectin(cFn)accumulation during alcohol-induced injury,and inv estigate whether increased cFn could have an effect on hepatocytes(HCs)by producing factors that could cont ribute to alcohol-induced liver injury.METHODS:HCs were isolated from rats fed a control or ethanol liquid diet for four to six weeks.Exogenous c Fn(up to 7.5 μg/mL)was added to cells cultured for 20 h,and viability(lactate dehydrogenase),apoptosis(caspase activity)and se cretion of proinflammat-ory cytokines(tumor ne c rosis fac tor alpha,TNF-α and interleukin 6,IL-6),mat rix metalloproteinases(MMPs)and their inhibitors(tissue inhibitors of metall-oproteinases,TIMPs)was det ermined.Degrad ation of iodinated cFn was det ermined 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 ethanolfed animals,and apoptosis was affected only at the higher concentration.Sec retion of MMPs,TIMPs,TNF-α and IL-6,however,was increased by exogenously added cFn,with HCs from ethanolfed animals showing increased susceptibility compared to the controls.CONCLUSION: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.
AIM: To examine the consequences of cellular f ibronectin (cFn) accumulation during alcohol-induced injury, and inv estigate whether increased cFn could have effect on hepatocytes (HCs) by producing factors that could cont ribute to alcohol-induced liver injury. METHODS : HCs were isolated from rats fed a control or ethanol liquid diet for four to six weeks. Exogenous c Fn up to 7.5 μg / mL was added to cells cultured for 20 h, and viability (lactate dehydrogenase), apoptosis (caspase activity ) and se cretion of proinflammat-ory cytokines (tumor ne c rosis fac tor alpha, TNF-α and interleukin 6, IL-6), mat rix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) det ermined. Degradtion of iodinated cFn was det ermined 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 ethanolf ed animals, and apoptosis was affected only at the higher concentration. SEC reactivity of MMPs, TIMPs, TNF-α and IL-6, however, was increased by exogenously added cFn, with HCs from ethanolfed animals showing increased susceptibility compared to the controls. CONCLUSION: 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.