H 2 S counteracts proinflammatory effects of LPS through modulation of multiple pathways in human cells.

Autor: Yurinskaya MM; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia.; Institute of Cell Biophysics RAS, PSCBR RAS, Puschino, 142290, Russia., Krasnov GS; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia., Kulikova DA; Koltzov Institute of Developmental Biology RAS, Moscow, 119991, Russia., Zatsepina OG; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia., Vinokurov MG; Institute of Cell Biophysics RAS, PSCBR RAS, Puschino, 142290, Russia., Chuvakova LN; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia., Rezvykh AP; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia.; Moscow Institute of Physics and Technology, Dolgoprudny, 141701, Russia., Funikov SY; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia., Morozov AV; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia., Evgen'ev MB; Engelhardt Institute of Molecular Biology RAS, Vavilov str. 32, Moscow, 119991, Russia. misha672011@yahoo.com.
Jazyk: angličtina
Zdroj: Inflammation research : official journal of the European Histamine Research Society ... [et al.] [Inflamm Res] 2020 May; Vol. 69 (5), pp. 481-495. Date of Electronic Publication: 2020 Mar 11.
DOI: 10.1007/s00011-020-01329-x
Abstrakt: Background: Hydrogen sulfide donors reduce inflammatory signaling in vitro and in vivo. The biological effect mediated by H 2 S donors depends on the kinetics of the gas release from the donor molecule. However, the molecular mechanisms of H 2 S-induced immunomodulation were poorly addressed. Here, we studied the effect of two different hydrogen sulfide (H 2 S)-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 H 2 S 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.
Databáze: MEDLINE
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