Antioxidant, N-acetyl-L-cysteine inhibits the expression of the collagen α2 (I) promoter in the activated human hepatic stellate cell line in the absence as well as the presence of transforming growth factor-β

Creators Segawa Makoto

Creators Kayano Kozo

Creators Sakaguchi Eiki

Creators Okamoto Mariko

Creators Sakaida Isao

Creators Okita Kiwamu

Although recent studies suggest the inhibitory property of N-acetyl-L-cysteine (NAC) on activation of hepatic stellate cell (HSC), the effects on once-activated HSCs are not well clarified. We investigated the influences of NAC on human-derived once-activated HSC line, LI90 with a focus on the collagen α2 (I) (COL1A2) promoter expression. Plasmid containing whole length of COL1A2 promoter linked to firefly luciferase gene and its various 5′-deletions were transiently transfected to LI90. The luciferase activity was determined with or without 10 mM of NAC in the absence or presence of 1 ng/ml of transforming growth factor (TGF)-β. The effects of NAC on generation of intracellular reactive oxygen species (ROS) in LI90 were also analyzed. As a result, NAC significantly (P<0.05) suppressed the COL1A2 promoter expression in the absence or presence of TGF-β. The expression was much more inhibited when used the deletion containing only AP-1/NF-κB binding sites than that including only three SP-1 binding sites. The ROS production was also comparably inhibited by NAC in both condition. These results indicated NAC suppressed, through its anti-oxidative action, the COL1A2 promoter expression in once-activated HSCs in the absence or presence of TGF-β at least partly by affecting the signal transduction cascade encompassing AP-1/NF-κB activation.

[ISSN]1386-6346

[NCID]AA11140867

info:doi/10.1016/S1386-6346(02)00089-X

[isVersionOf] [URI]http://www.sciencedirect.com/science/journal/13866346