Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H₂S-Producing Enzymes in Multiple Sclerosis

• Main Authors: Milica Lazarević (Author), Giuseppe Battaglia (Author), Bojan Jevtić (Author), Neda Djedovic (Author), Valeria Bruno (Author), Eugenio Cavalli (Author), Đorđe Miljković (Author), Ferdinando Nicoletti (Author), Miljana Momčilović (Author), Paolo Fagone (Author)
• Format: Book
• Published: MDPI AG, 2020-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

10.3390/antiox9070608
2076-3921