Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of [H.sub.2]S-Producing Enzymes in Multiple Sclerosis

• Published in: Antioxidants Vol. 9; no. 7
• Main Authors: Lazarevic, Milica, Battaglia, Giuseppe, Jevtic, Bojan, Djedovic, Neda, Bruno, Valeria, Cavalli, Eugenio, Miljkovic, Dorde, Nicoletti, Ferdinando, Momcilovic, Miljana, Fagone, Paolo
• Format: Journal Article
• Language: English
• Published: MDPI AG 01-07-2020
• Subjects: Gene expression; Genetic aspects; Health aspects; Hydrogen sulfide; Multiple sclerosis; Italy
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox9070608

The aim of this study was to examine the in vitro effects of the slow-releasing [H.sub.2]S 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-p expression and production in dendritic cells and significantly reduced IFN-[gamma] 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.sup.+] 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 [H.sub.2]S-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.