Differential effects between tauroursodeoxycholic and taurochenodeoxycholic acids in hepatic fibrosis: An assessment by primary cultured Ito and Kupffer cells from the rat liver*

ABSTRACT 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 the cell proliferation and collagen formation of primary cultured Ito cells that were incubated with a Kupffer cell conditioned medium (KCCM) treated with either taurochenodeoxycholic acid (TCDCA) or tauroursodeoxycholic acid (TUDCA) in short‐term (8 h) or long‐term (48 h) cultures. KCCM treated with TCDCA (100 μmol/L) but not with TUDCA increased cell proliferation of Ito cells in short‐term cultures and also partially elevated collagen formation by Ito cells in long‐term cultures. The release of tumour necrosis factor‐α (TNFα) from Kupffer cells was increased by TCDCA in short‐term cultures, but not in long‐term cultures. The release of transforming growth factor‐β 1 (TGFβ 1 ) from Kupffer cells was increased by TCDCA in long‐term cultures, but not in the short‐term cultures. TUDCA showed no significant effect on the release of TNFα and TGFβ 1 from Kupffer cells. TUDCA or TCDCA itself showed no direct effect on the cell proliferation and 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 without endotoxaemia.