Vitamin D ameliorates stress ligand expression elicited by free fatty acids in hepatic stellate cells

Background/Aims: Hepatic stellate cells (HSC) play an important role as the major source of fibrillar and nonfibrillar matrix proteins in the process of liver fibrosis. Natural killer (NK) cells have an antifibrotic effect through killing activated HSC. Major histocompatibilitiy complex class I (MHC-I)- related molecules, MICA and MICB, function as ligands for the NKG2D receptor and play a role in HSC susceptibility to NK cells during hepatic inflammation. The aim of this study was to investigate the effect of vitamin D2 and free fatty acids (FFA) on stress ligands and profibrotic activity in LX-2 cells and human primary HSC. Methods: LX2 cells and primary human HSC were treated with Vitamin D2 (10–6M) and FFA at different concentrations (0.25mM, 0.5mM, 1mM) for 24 hours and expression of the stress ligands MICA/B as well as TGF-β, α-SMA, COL1α were assessed by quantitative real time PCR. Results: Treatment of cells with 0.5mM and 1mM FFA induced α-SMA and TGF-β expression in LX2 cells. Moreover 1mM FFA led to increased expression of MICA. Surprisingly COL1α expression was reduced after addition of FFA. MICA/B expression in primary HSC was not affected by FFA. VD2 treatment significantly downregulated the FFA induced expression of TGF-β and α-SMA LX-2 cells. In HSC a significant decrease of MICA/B mRNA by VD2, independent of FFA treatment was detectable. Conclusion: These results indicate that VD2 can reduces inflammatory and profibrogenic activity of stellate cells in vitro. Although reduction of MICA/B by VD may not be beneficial in terms of reducing activated HSC numbers in patients with fibrosis.

MICA/B - NKG2D ligands - hepatic stellate cells - vitamin D