title: Immunoregulatory effects of glutathione during mesenchymal stem cell differentiation to hepatocyte-like cells.
abstract: BACKGROUND
  The role of mesenchymal stem cell in cellular therapy is the subject of interest for many researchers. The differentiation potential of MSCs and abilities in modulations of the recipient's immune system makes them important cells in tissue regenerative studies. MSCs by releasing the proinflammatory cytokines play important role in immunomodulatory systems; however the signaling pathways for releasing of these mediators are not well understood. Glutathione has been shown to play a role in modulation of cytokines in hepatogenic differentiation.
  
  
  OBJECTIVE
  In the current study we aimed to investigate the effects of buthionine sulfoximine (BSO, inhibitor for glutathione synthesis) and N-acetylecystin (NAC, an inhibitor for ROS generation) on proinflammatory cytokines production in a hepatogenic differentiation model.
  
  
  RESULTS
  BSO and NAC significantly decreased IL-6 and TNF-α levels at 14 days of differentiation, whereas, NAC decreased the levels of IL-8 at days 2 and 14 of differentiation. Moreover, intracellular glutathione level during the differentiation was depleted.
  
  
  CONCLUSIONS
  Our current study suggests a novel role of GSH as an immunopharmacological regulatory molecule during hepatogenic differentiation. Finally, this information may shed some light on the understanding of MSCs responses in transplantation and cell therapy in diseases such as chronic hepatic diseases.
authors.affiliation: Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran, e-mail: allameha@modares.ac.ir.
authors.forename: Hamid-Reza
authors.initials: HR
authors.lastname: Ahmadi-Ashtiani
authors.forename: Abdolamir
authors.initials: A
authors.lastname: Allameh
authors.forename: Hossein
authors.initials: H
authors.lastname: Rastegar
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
authors.forename: Zahir
authors.initials: Z
authors.lastname: Saraf
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D048091:Guided Tissue Regeneration; D022781:Hepatocytes / Q000166:cytology*; D006801:Humans; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000494:pharmacology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; D005978:Glutathione; D000111:Acetylcysteine