title: Vitamin D ameliorates stress ligand expression elicited by free fatty acids in the hepatic stellate cell line LX-2.
abstract: OBJECTIVE
  Hepatic stellate cells play an important role as the major source of fibrillar and non-fibrillar matrix proteins in the process of liver fibrosis. Natural killer cells have an anti-fibrotic effect through the killing of activated hepatic stellate cells. Major histocompatibility complex class I-related molecules, MICA and MICB, function as ligands for the NKG2D receptor and play an important role in hepatic stellate cells susceptibility to natural killer cells during hepatic inflammation. The aim of this study was therefore to investigate the effect of vitamin D2 and free fatty acids on stress ligands and pro-fibrotic activity in LX-2 cells and human primary hepatic stellate cells.
  
  
  METHODS
  LX-2 cells and primary human hepatic stellate cells were treated with vitamin D2 (10-6 M) and free fatty acids at different concentrations (0.25 mM, 0.5 mM, and 1 mM) for 24 hours, and expressions of the stress ligands MICA/B as well as of transforming growth factor-β, α-smooth muscle actin and collagen 1α were assessed by quantitative real time-polymerase chain reaction.
  
  
  RESULTS
  Treatment of cells with 0.5 mM and 1 mM free fatty acids induced α-smooth muscle actin and transforming growth factor-β expression in LX-2 cells. Moreover, 1 mM free fatty acids resulted in increased expression of MICA. Surprisingly, collagen 1α expression was reduced after addition of free fatty acids. MICA/B expression in primary hepatic stellate cells was not affected by free fatty acids treatment. Vitamin D2 treatment significantly downregulated the free fatty acids-induced expression of transforming growth factor-β and α-smooth muscle actin in LX-2 cells. Further, in hepatic stellate cells, a significant decrease in MICA/B mRNA with vitamin D2, independent of free fatty acids treatment, was detectable.
  
  
  CONCLUSIONS
  These results indicate that vitamin D2 may reduce inflammatory and pro-fibrogenic activity of stellate cells in vitro.
authors.affiliation: University Hospital Essen Hufelandstr., Essen, Germany.
authors.forename: Seyda
authors.initials: S
authors.lastname: Seydel
authors.forename: Anja
authors.initials: A
authors.lastname: Beilfuss
authors.forename: Alişan
authors.initials: A
authors.lastname: Kahraman
authors.forename: Kıymet
authors.initials: K
authors.lastname: Aksoy
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Hikmet
authors.initials: H
authors.lastname: Akkiz
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D004872:Ergocalciferols / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D024042:Collagen Type I; D004872:Ergocalciferols; D005230:Fatty Acids, Nonesterified; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A; C098080:MICB antigen; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta