Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H<sub>2</sub>S-Producing Enzymes in Multiple Sclerosis
Milica Lazarević,
Giuseppe Battaglia,
Bojan Jevtić,
Neda Djedovic,
Valeria Bruno,
Eugenio Cavalli,
Đorđe Miljković,
Ferdinando Nicoletti,
Miljana Momčilović,
Paolo Fagone
Affiliations
Milica Lazarević
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia
Giuseppe Battaglia
Department of Physiology and Pharmacology, Sapienza University, Piazzale A. Moro, 5, 00185 Rome, Italy
Bojan Jevtić
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia
Neda Djedovic
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia
Valeria Bruno
Department of Physiology and Pharmacology, Sapienza University, Piazzale A. Moro, 5, 00185 Rome, Italy
Eugenio Cavalli
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Đorđe Miljković
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia
Ferdinando Nicoletti
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
Miljana Momčilović
Department of Immunology, Institute for Biological Research “Siniša Stanković”—National Institute of Republic of Serbia, University of Belgrade, Despota Stefana 142, 11060 Belgrade, Serbia
Paolo Fagone
Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 89, 95123 Catania, Italy
The aim of this study was to examine the in vitro effects of the slow-releasing H2S donor GYY4137 on the immune cells involved in the pathogenesis of the central nervous system (CNS) autoimmune disease, multiple sclerosis (MS). GYY4137 specifically potentiated TGF-β expression and production in dendritic cells and significantly reduced IFN-γ and IL-17 production in the lymph node and spinal cord T cells obtained from mice immunized with CNS antigens. Both the proportion of FoxP3+ regulatory CD4+ T cells in the lymph node cells, and the percentage of IL-17+ CD4+ T cells in the spinal cord cells were reduced upon culturing with GYY4137. Interestingly, the peripheral blood mononuclear cells obtained from the MS patients had a lower expression of the H2S-producing enzyme, 3-mercaptopyruvate-sulfurtransferase (MPST), in comparison to those obtained from healthy donors. A significant inverse correlation between the expression of MPST and several pro-inflammatory factors was also observed. Further studies on the relevance of the observed results for the pathogenesis and therapy of MS are warranted.
