H2S counteracts proinflammatory effects of LPS through modulation of multiple pathways in human cells
- 11 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Inflammation Research
- Vol. 69 (5), 481-495
- https://doi.org/10.1007/s00011-020-01329-x
Abstract
Background Hydrogen sulfide donors reduce inflammatory signaling in vitro and in vivo. The biological effect mediated by H2S donors depends on the kinetics of the gas release from the donor molecule. However, the molecular mechanisms of H2S-induced immunomodulation were poorly addressed. Here, we studied the effect of two different hydrogen sulfide (H2S)-producing agents on the generation of the LPS-induced inflammatory mediators. Importantly, we investigated the transcriptomic changes that take place in human cells after the LPS challenge, combined with the pretreatment with a slow-releasing H2S donor-GYY4137. Methods We investigated the effects of GYY4137 and sodium hydrosulfide on the release of proinflammatory molecules such as ROS, NO and TNF-α from LPS-treated human SH-SY5Y neuroblastoma and the THP-1 promonocytic cell lines. Transcriptomic and RT-qPCR studies using THP-1 cells were performed to monitor the effects of the GYY4137 on multiple signaling pathways, including various immune-related and proinflammatory genes after combined action of LPS and GYY4137. Results The GYY4137 and sodium hydrosulfide differed in the ability to reduce the production of the LPS-evoked proinflammatory mediators. The pre-treatment with GYY4137 resulted in a drastic down-regulation of many TNF-α effectors that are induced by LPS treatment in THP-1 cells. Furthermore, GYY4137 pretreatment of LPS-exposed cells ameliorates the LPS-mediated induction of multiple pro-inflammatory genes and decreases expression of immunoproteasome genes. Besides, in these experiments we detected the up-regulation of several important pathways that are inhibited by LPS. Conclusion Based on the obtained results we believe that our transcriptomic analysis significantly contributes to the understanding of the molecular mechanisms of anti-inflammatory and cytoprotective activity of hydrogen sulfide donors, and highlights their potential against LPS challenges and other forms of inflammation.Keywords
Funding Information
- Russian Science Foundation (17-74-30030)
- Russian grant Program for Basic Science (19-04-00109)
This publication has 54 references indexed in Scilit:
- The complex effects of the slow‐releasing hydrogen sulfide donor GYY4137 in a model of acute joint inflammation and in human cartilage cellsJournal of Cellular and Molecular Medicine, 2013
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- clusterProfiler: an R Package for Comparing Biological Themes Among Gene ClustersOMICS: A Journal of Integrative Biology, 2012
- LPS-Induced Formation of Immunoproteasomes: TNF-α and Nitric Oxide Production are Regulated by Altered Composition of Proteasome-Active SitesCell Biochemistry and Biophysics, 2011
- CARHSP1 Is Required for Effective Tumor Necrosis Factor Alpha mRNA Stabilization and Localizes to Processing Bodies and ExosomesMolecular and Cellular Biology, 2011
- The Effect of Hydrogen Sulfide Donors on Lipopolysaccharide-Induced Formation of Inflammatory Mediators in MacrophagesAntioxidants and Redox Signaling, 2010
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- KEY INFLAMMATORY SIGNALING PATHWAYS ARE REGULATED BY THE PROTEASOMEShock, 2006
- Lipopolysaccharide signaling in endothelial cellsLaboratory Investigation, 2006
- Exogenous heat shock protein 70 mediates sepsis manifestations and decreases the mortality rate in ratsCell Stress and Chaperones, 2006