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Immunoregulatory Effects of Glutathione During Mesenchymal Stem Cell Differentiation to Hepatocyte-Like Cells

Author(s): Hamid-Reza Ahmadi-Ashtiani | Abdolamir Allameh | Hossein Rastegar | Esmaeil Mortaz | Zahir Saraf

Journal: Iranian Journal of Immunology
ISSN 1735-1383

Volume: 9;
Issue: 3;
Start page: 175;
Date: 2012;
Original page

Keywords: Differentiation | Glutathione | Modification | Interleukins | Stem Cells | Tumor Necrosis Factor

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 re-generative 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 glu-tathione synthesis) and N-acetylecystin (NAC, an inhibitor for ROS generation) on pro-inflammatory cytokines production in a hepatogenic differentiation model. Results: BSO and NAC significantly decreased IL-6 and TNF-α levels at 14 days of differentia-tion, whereas, NAC decreased the levels of IL-8 at days 2 and 14 of differentiation. Moreover, intracellular glutathione level during the differentiation was depleted. Con-clusion: 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.

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