DIFFERENTIAL-EFFECTS BETWEEN TAUROURSODEOXYCHOLIC AND TAUROCHENODEOXYCHOLIC ACIDS IN HEPATIC-FIBROSIS - AN ASSESSMENT BY PRIMARY CULTURED ITO AND KUPFFER CELLS FROM THE RAT-LIVER

The pathogenesis of hepatic fibrosis in cholestasis is still unknown, except for endotoxaemia. There is a possibility that the elevation of serum bile acids in cholestasis may play an important role in hepatic fibrogenesis due to a reaction to perisinusoidal cells, such as Ito or Kupffer cells. To assess the effects of bile acids, we investigated t he cell proliferation and collagen formation of primary cultured Ito c ells that were incubated with a Kupffer cell conditioned medium (KCCM) treated with either taurochenodeoxycholic acid (TCDCA) or tauroursode oxycholic acid (TUDCA) in short-term (8 h) or long-term (48 h) culture s. KCCM treated with TCDCA (100 mu mol/L) but not with TUDCA increased cell proliferation of Ito cells in short-term cultures and also parti ally elevated collagen formation by Ito cells in long-term cultures. T he release of tumour necrosis factor-alpha (TNF alpha) from Kupffer ce lls was increased by TCDCA in short-term cultures, but not in long-ter m cultures. The release of transforming growth factor-beta(1) (TGF bet a(1)) from Kupffer cells was increased by TCDCA in long-term cultures, bur: not in the short-term cultures. TUDCA showed no significant effe ct on the release of TNF alpha and TGF beta(1) from Kupffer cells. TUD CA or TCDCA itself showed no direct effect on the cell proliferation a nd collagen formation of Ito cells. In conclusion, these findings are thus considered to show the potentially important role of TCDCA on the development of hepatic fibrosis in the early phase of cholestasis wit hout endotoxaemia.