H2S counteracts proinflammatory effects of LPS through modulation of multiple pathways in human cells

Yurinskaya, M. M.; Krasnov, George S.; Куликова, Д. А.; Zatsepina, Olga G.; Винокуров, М. Г.; Chuvakova, Lyubov N.; Rezvykh, Alexander P.; Funikov, Sergei; Morozov, Alexey; Евгеньев, М. Б.

doi:10.1007/s00011-020-01329-x

Cited by 24 publications

(32 citation statements)

References 53 publications

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“…Tumor necrosis factor-α (TNF-α) is considered a pivotal cytokine in joint inflammation and hypernociception and initiates catabolic responses in the chondrocyte, including the generation of ROS and the activation of iNOS and COX-2 expression [ 10 , 52 , 53 , 54 ]. Interestingly, ATB-346, a novel H 2 S-releasing naproxen, more efficiently reduces TNF-α release in a rat model of arthritis [ 55 ], and GYY-4137 inhibits the expression of effectors of the TNF pathway [ 56 ]. Thus, the inhibition of the production of these mediators has been associated with the chondroprotective effect of H 2 S [ 27 , 55 , 56 ], and subsequently it could be responsible for the lesser OA severity and pain observed in our model under GYY-4137 treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, ATB-346, a novel H 2 S-releasing naproxen, more efficiently reduces TNF-α release in a rat model of arthritis [ 55 ], and GYY-4137 inhibits the expression of effectors of the TNF pathway [ 56 ]. Thus, the inhibition of the production of these mediators has been associated with the chondroprotective effect of H 2 S [ 27 , 55 , 56 ], and subsequently it could be responsible for the lesser OA severity and pain observed in our model under GYY-4137 treatment.…”

Section: Discussionmentioning

confidence: 99%

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Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis

Vaamonde‐García

Burguera

Vela-Anero

et al. 2020

IJMS

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Osteoarthritis (OA) is the most common articular chronic disease. However, its current treatment is limited and mostly symptomatic. Hydrogen sulfide (H2S) is an endogenous gas with recognized physiological activities. The purpose here was to evaluate the effects of the intraarticular administration of a slow-releasing H2S compound (GYY-4137) on an OA experimental model. OA was induced in Wistar rats by the transection of medial collateral ligament and the removal of the medial meniscus of the left joint. The animals were randomized into three groups: non-treated and intraarticularly injected with saline or GYY-4137. Joint destabilization induced articular thickening (≈5% increment), the loss of joint mobility and flexion (≈12-degree angle), and increased levels of pain (≈1.5 points on a scale of 0 to 3). Animals treated with GYY-4137 presented improved motor function of the joint, as well as lower pain levels (≈75% recovery). We also observed that cartilage deterioration was attenuated in the GYY-4137 group (≈30% compared with the saline group). Likewise, these animals showed a reduced presence of pro-inflammatory mediators (cyclooxygenase-2, inducible nitric oxide synthase, and metalloproteinase-13) and lower oxidative damage in the cartilage. The increment of the nuclear factor-erythroid 2-related factor 2 (Nrf-2) levels and Nrf-2-regulated gene expression (≈30%) in the GYY-4137 group seem to be underlying its chondroprotective effects. Our results suggest the beneficial impact of the intraarticular administration of H2S on experimental OA, showing a reduced cartilage destruction and oxidative damage, and supporting the use of slow H2S-producing molecules as a complementary treatment in OA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis

Vaamonde‐García

Burguera

Vela-Anero

et al. 2020

IJMS

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“…Conversely, H 2 S can also exhibit anti-inflammatory functions by downregulating pro-inflammatory factors. For example, the H 2 S donor GYY4137 ( Li et al., 2008 ), a slow releaser of H 2 S, and NaHS were shown to downregulate expression of the pro-inflammatory mediators TNF-α, ROI, and •NO in LPS-treated neuroblastoma cells and macrophage cells, illustrating the anti-inflammatory and cytoprotective role of H 2 S in LPS-mediated inflammation ( Whiteman et al., 2010b ; Yurinskaya et al., 2020 ). Also, the H 2 S-releasing compound ATB-429 reduced colitis-induced inflammation in mice by reducing granulocyte infiltration into colon tissue ( Fiorucci et al., 2007 ).…”

Section: The Physiological Importance Of H 2 Smentioning

confidence: 99%

The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

Rahman

Glasgow

Nadeem

et al. 2020

Front. Cell. Infect. Microbiol.

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For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

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“…In recent decades, our laboratory has conducted comprehensive studies of the protective properties of recombinant human Hsp70 and various H 2 S donors at the cellular and organismal (mice, rats, Drosophila ) levels [ 6 , 11 , 12 , 23 , 28 , 29 , 30 ]. Our studies showed that both H 2 S donors and rHsp70 show a significant anti-inflammatory effect in all the model systems we used (cell cultures, model organisms), reducing the level of the main inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

The Effects of H2S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo

et al. 2022

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The ongoing epidemic caused by SARS-CoV-2 infection led to the search for fundamentally new ways and means to combat inflammation and other pathologies caused by this virus. Using a cellular model of lipopolysaccharide (LPS)-induced sepsis (human promonocytes), we showed that both a hydrogen sulfide donor (sodium thiosulfate, STS) and a recombinant Heat shock protein 70 (rHsp70) effectively block all major inflammatory mediators when administrated before and after LPS challenge. The protective anti-inflammatory effect of rHsp70 and H2S was also confirmed in vivo using various animal models of pneumonia. Specifically, it was found that rHsp70 injections prevented the development of the acute respiratory distress syndrome in highly pathogenic pneumonia in mice, increased animal survival, and reduced the number of Programmed death-1 (PD-1)-positive T-lymphocytes in peripheral blood. Based on our model experiments we developed a combined two-phase therapeutic approach for the treatment of COVID-19 patients. This procedure includes the inhalation of hot helium–oxygen mixtures for induction of endogenous Hsp70 in the first phase and STS inhalation in the second phase. The use of this approach has yielded positive results in COVID-19 patients, reducing the area of lung lesions, restoring parameters of innate immunity and T-cell immune response against coronavirus infection, and preventing the development of pulmonary fibrosis and immune exhaustion syndrome.

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H2S counteracts proinflammatory effects of LPS through modulation of multiple pathways in human cells

Cited by 24 publications

References 53 publications

Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis

Intraarticular Administration Effect of Hydrogen Sulfide on an In Vivo Rat Model of Osteoarthritis

The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

The Effects of H2S and Recombinant Human Hsp70 on Inflammation Induced by SARS and Other Agents In Vitro and In Vivo

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