Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis
Abstract
:1. Introduction
2. Materials and Methods
2.1. In Vitro, In Vivo and Ex Vivo Studies
2.1.1. Cells and Cell Cultures
2.1.2. Cell Viability Assay
2.1.3. Cytokine Level Measurement
2.1.4. Cytometry
2.1.5. Reverse Transcription—Real-Time Polymerase Chain Reaction
2.2. In Silico Studies
2.2.1. Analysis of the Expression Levels of H2S-Producing Enzymes in Human CD4+ T Cell Subset
2.2.2. Analysis of the Expression Levels of H2S-Producing Enzymes in PBMCs from MS Patients
2.2.3. Computational Deconvolution of Immune Cells Population
2.3. Statistical Analysis
3. Results
3.1. In Vitro, In Vivo and Ex Vivo Studies
3.1.1. Effects of GYY4137 on Dendritic Cells
3.1.2. Effects of GYY4137 on Mouse Lymph Node T cells
3.1.3. Effects of GYY4137 on the Rat Lymph Node T Cells
3.1.4. Effects of GYY4137 on Spinal Cord T Cells
3.2. In Silico Studies
3.2.1. Expression of H2S-Producing Enzymes in Human CD4+ T Cell Subsets
3.2.2. Expression of H2S-Producing Enzymes in PBMCs from Multiple Sclerosis Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Pearson r | 95% Confidence Interval | R Squared | p Value | |
---|---|---|---|---|
MPST vs. TNF | −0.6234 | −0.8112 to −0.3189 | 0.3886 | 0.0005 |
MPST vs. IL2 | −0.3639 | −0.6536 to 0.01865 | 0.1325 | 0.0620 |
MPST vs. IL6 | −0.6283 | −0.8140 to −0.3261 | 0.3947 | 0.0004 |
MPST vs. IL17A | −0.1955 | −0.5357 to 0.1993 | 0.0382 | 0.3285 |
MPST vs. IFNG | −0.548 | −0.7681 to −0.2122 | 0.3003 | 0.0031 |
MPST vs. IL12A | 0.3633 | −0.01940 to 0.6531 | 0.1320 | 0.0625 |
MPST vs. IL23A | −0.492 | −0.7347 to −0.1378 | 0.2421 | 0.0091 |
MPST vs. IL10 | −0.3544 | −0.6472 to 0.02964 | 0.1256 | 0.0697 |
MPST vs. CCR7 | −0.6298 | −0.8148 to −0.3284 | 0.3967 | 0.0004 |
MPST vs. CD40LG | −0.6226 | −0.8108 to −0.3177 | 0.3876 | 0.0005 |
MPST vs. IL2RA | −0.4755 | −0.7246 to −0.1166 | 0.2261 | 0.0122 |
MPST vs. SELL | 0.4422 | 0.07476 to 0.7039 | 0.1956 | 0.0209 |
MPST vs. CD69 | −0.6878 | −0.8465 to −0.4167 | 0.4730 | <0.0001 |
MPST vs. IDO1 | −0.4533 | −0.7109 to −0.08856 | 0.2055 | 0.0176 |
MPST vs. HMOX1 | 0.4613 | 0.09860 to 0.7158 | 0.2128 | 0.0154 |
MPST vs. ARG1 | −0.2147 | −0.5498 to 0.1800 | 0.0461 | 0.2822 |
MPST vs. NOS2 | −0.1639 | −0.5120 to 0.2305 | 0.0269 | 0.4140 |
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Lazarević, M.; Battaglia, G.; Jevtić, B.; Djedovic, N.; Bruno, V.; Cavalli, E.; Miljković, Đ.; Nicoletti, F.; Momčilović, M.; Fagone, P. Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis. Antioxidants 2020, 9, 608. https://doi.org/10.3390/antiox9070608
Lazarević M, Battaglia G, Jevtić B, Djedovic N, Bruno V, Cavalli E, Miljković Đ, Nicoletti F, Momčilović M, Fagone P. Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis. Antioxidants. 2020; 9(7):608. https://doi.org/10.3390/antiox9070608
Chicago/Turabian StyleLazarević, Milica, Giuseppe Battaglia, Bojan Jevtić, Neda Djedovic, Valeria Bruno, Eugenio Cavalli, Đorđe Miljković, Ferdinando Nicoletti, Miljana Momčilović, and Paolo Fagone. 2020. "Upregulation of Tolerogenic Pathways by the Hydrogen Sulfide Donor GYY4137 and Impaired Expression of H2S-Producing Enzymes in Multiple Sclerosis" Antioxidants 9, no. 7: 608. https://doi.org/10.3390/antiox9070608