期刊
JOURNAL OF HEPATOLOGY
卷 33, 期 1, 页码 49-58出版社
MUNKSGAARD INT PUBL LTD
DOI: 10.1016/S0168-8278(00)80159-2
关键词
apoptosis; collagen; fibrosis; hepatic stellate cell; NF kappa B; TNF alpha
资金
- NIAAA NIH HHS [AA-10459] Funding Source: Medline
- NIDDK NIH HHS [DK-34987] Funding Source: Medline
- NIGMS NIH HHS [GM-41804] Funding Source: Medline
Background/Aims: Activation of the transcription factor NF kappa B has been demonstrated in activated hepatic stellate cells (HSCs), We investigated the role of NF kappa B in proliferation, in activation, and in TNF alpha-induced apoptosis of HSCs. Methods: NF kappa B activation was inhibited using an adenovirus expressing an I kappa B dominant negative protein (Ad5I kappa B) in both quiescent and activated HSCs. Quiescent HSCs were infected with Ad5I kappa B or an adenovirus expressing beta-galactosidase (Ad5LacZ), The cells were cultured for 7 days, HSCs activation was determined by cell morphology, smooth muscle alpha-actin (alpha-sma) expression, and steady-state mRNA levers of alpha 1(I) collagen as assessed by Western blot and RNase protection assay, respectively, Proliferation was determined in culture-activated HSCs by H-3-thymidine incorporation and direct cell counting, Apoptosis was analyzed by infecting quiescent or activated HSCs with Ad5I kappa B or Ad5LacZ, and then treating with TNF alpha. Apoptosis was demonstrated by determining cell number, assessing nuclear morphology, TUNEL assay and caspase 3 activity. Results: After 7 days in culture no differences were noted between the Ad5I kappa B- and the Ad5LacZ-infected cells in the morphology, alpha-sma expression or in alpha 1(I) collagen mRNA levels, Ad5I kappa B infection did not modify proliferation in activated HSCs, TNFa induced apoptosis only in Ad5I kappa B-infected activated, but not quiescent HSCs, Apoptosis was initially demonstrated 12 h after exposure to TNF alpha. Twenty-four h after the TNF alpha treatment, 60% of the activated HSCs were apoptotic. Conclusion: NF kappa B activity is not required for proliferation or activation of HSCs; however, NF kappa B protects activated HSCs against TNF alpha-induced apoptosis.
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