High concentrations of hydrogen sulphide elevate the expression of a series of pro-inflammatory genes in fibroblast-like synoviocytes derived from rheumatoid and osteoarthritis patients

Kloesch, Burkhard; Liszt, Melissa; Krehan, Daniela; Broell, Johann; Kiener, Hans P.; Steiner, Günter

doi:10.1016/j.imlet.2011.10.004

Cited by 49 publications

(35 citation statements)

References 35 publications

(36 reference statements)

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“…Surprisingly, NaHS increased phosphorylation of Akt1/2 by 50–60% (Fig. B and D), an effect that was also observed in unstimulated NaHS‐treated cells in which, in line with previous observations , activation of ERK2 and its downstream target MSK2 was also seen (Fig. C).…”

Section: Resultssupporting

confidence: 90%

Hydrogen sulphide decreases IL‐1β‐induced activation of fibroblast‐like synoviocytes from patients with osteoarthritis

Sieghart

Liszt

Wanivenhaus

et al. 2014

J Cellular Molecular Medi

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Balneotherapy employing sulphurous thermal water is still applied to patients suffering from diseases of musculoskeletal system like osteoarthritis (OA) but evidence for its clinical effectiveness is scarce. Since the gasotransmitter hydrogen sulphide (H2S) seems to affect cells involved in degenerative joint diseases, it was the objective of this study to investigate the effects of exogenous H2S on fibroblast-like synoviocytes (FLS), which are key players in OA pathogenesis being capable of producing pro-inflammatory cytokines and matrix degrading enzymes. To address this issue primary FLS derived from OA patients were stimulated with IL-1β and treated with the H2S donor NaHS. Cellular responses were analysed by ELISA, quantitative real-time PCR, phospho-MAPkinase array and Western blotting. Treatment-induced effects on cellular structure and synovial architecture were investigated in three-dimensional extracellular matrix micromasses. NaHS treatment reduced both spontaneous and IL-1β-induced secretion of IL-6, IL-8 and RANTES in different experimental settings. In addition, NaHS treatment reduced the expression of matrix metallo-proteinases MMP-2 and MMP-14. IL-1β induced the phosphorylation of several MAPkinases. NaHS treatment partially reduced IL-1β-induced activation of several MAPK whereas it increased phosphorylation of pro-survival factor Akt1/2. When cultured in spherical micromasses, FLS intentionally established a synovial lining layer-like structure; stimulation with IL-1β altered the architecture of micromasses leading to hyperplasia of the lining layer which was completely inhibited by concomitant exposure to NaHS. These data suggest that H2S partially antagonizes IL-1β stimulation via selective manipulation of the MAPkinase and the PI3K/Akt pathways which may encourage development of novel drugs for treatment of OA.

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Section: Resultssupporting

confidence: 90%

Hydrogen sulphide decreases IL‐1β‐induced activation of fibroblast‐like synoviocytes from patients with osteoarthritis

Sieghart

Liszt

Wanivenhaus

et al. 2014

J Cellular Molecular Medi

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“…Similarly, synovial fluid H 2 S levels are elevated relative to disease controls in patients with rheumatoid arthritis (Whiteman et al 2010c) and inflammatory joint disease (Whiteman and Winyard 2011). Early studies generally showed inhibition of endogenous H 2 S synthesis attenuated pro-inflammatory signalling in vitro and inflammation in vivo (reviewed in Whiteman and Winyard (2011)), although it should be noted that pharmacological inhibitors of CSE, CBS and 3-MST are non-specific necessitating their use at very high concentrations (reviewed in detail in ) and the addition of NaSH to cultured cells in vitro (Whiteman et al 2010b;Zhang et al 2008;Zhi et al 2007;Kloesch et al 2012a, b). Similarly, administration of NaSH to laboratory animals either induced systemic inflammation directly or exacerbated inflammation (Li et al 2005;Bhatia et al 2005Bhatia et al , 2006Tamizhselvi et al 2007;Ang et al 2010Ang et al , 2011Badiei et al 2013).…”

Section: Gyy4137: Anti-inflammatory Effectsmentioning

confidence: 99%

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

Whiteman

Perry

Zhou³

et al. 2015

Handbook of Experimental Pharmacology

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Hydrogen sulfide is rapidly emerging as a key physiological mediator and potential therapeutic tool in numerous areas such as acute and chronic inflammation, neurodegenerative and cardiovascular disease, diabetes, obesity and cancer. However, the vast majority of the published studies have employed crude sulfide salts such as sodium hydrosulfide (NaSH) and sodium sulfide (Na2S) as H2S "donors" to generate H2S. Although these salts are cheap, readily available and easy to use, H2S generated from them occurs as an instantaneous and pH-dependent dissociation, whereas endogenous H2S synthesis from the enzymes cystathionine γ-lyase, cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase is a slow and sustained process. Furthermore, sulfide salts are frequently used at concentrations (e.g. 100 μM to 10 mM) far in excess of the levels of H2S reported in vivo (nM to low μM). For the therapeutic potential of H2S is to be properly harnessed, pharmacological agents which generate H2S in a physiological manner and deliver physiologically relevant concentrations are needed. The phosphorodithioate GYY4137 has been proposed as "slow-release" H2S donors and has shown promising efficacy in cellular and animal model diseases such as hypertension, sepsis, atherosclerosis, neonatal lung injury and cancer. However, H2S generation from GYY4137 is inefficient necessitating its use at high concentrations/doses. However, structural modification of the phosphorodithioate core has led to compounds (e.g. AP67 and AP105) with accelerated rates of H2S generation and enhanced biological activity. In this review, the therapeutic potential and limitations of GYY4137 and related phosphorodithioate derivatives are discussed.

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“…These findings suggest that H 2 S is an endogenous mediator of the development of hindpaw local inflammation. Recent reports in the literature in human patients point to a role of H 2 S in rheumatoid arthritis, but there is a difference of opinion as to the pro-versus antiinflammatory action of H 2 S (Fox et al 2012;Kloesch et al 2012). …”

Section: Joint Inflammation/arthritismentioning

confidence: 99%

H2S and Inflammation: An Overview

Bhatia

2015

Handbook of Experimental Pharmacology

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Inflammation is a response to traumatic, infectious, post-ischemic, toxic, or autoimmune injury. However, uncontrolled inflammation can lead to disease, and inflammation is now believed to be responsible for several disease conditions. Research in our laboratory has shown that hydrogen sulfide (H2S) acts as a novel mediator of inflammation. At present, work in several research groups worldwide is focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions. Most of this research involved working with animal models of disease and in vitro systems. Recent research, however, points to a role of H2S in clinical inflammatory disease as well. This chapter describes our current understanding of the role of H2S in inflammation.

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High concentrations of hydrogen sulphide elevate the expression of a series of pro-inflammatory genes in fibroblast-like synoviocytes derived from rheumatoid and osteoarthritis patients

Cited by 49 publications

References 35 publications

Hydrogen sulphide decreases IL‐1β‐induced activation of fibroblast‐like synoviocytes from patients with osteoarthritis

Hydrogen sulphide decreases IL‐1β‐induced activation of fibroblast‐like synoviocytes from patients with osteoarthritis

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

H2S and Inflammation: An Overview

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