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

Abstract

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.

Hydrogen Medicine Therapy: An Effective and Promising Novel Treatment for Multiple Organ Dysfunction Syndrome (MODS) Induced by Influenza and Other Viral Infections Diseases?

“…Since persistent tissue damage, MODS and high mortality rate are highly associated with oxidative stress and cytokine storm induced by influenza and other severe viral infections hydrogen can significantly reduce oxidative stress and restrain excessive production of cytokines [9, [57][58][59][60]. We hypothesize that hydrogen can be potentially effective for MODS induced by influenza and other viral infectious diseases.…”

Estudo dos efeitos do composto GYY-4137, um doador de sulfeto de hidrogênio (H₂S), na sinovite aguda induzida por carragenina na articulação temporomandibular de ratos.

“…Estudos realizados por Nozawa-Inoue et al (2003) demonstraram que ocorre aumento de células do tipo A na inflamação da membrana sinovial e que essas células são capazes de produzir substâncias pró-inflamatórias como o óxido nítrico (NO) produzido pela enzima óxido nítrico sintase induzível (iNOS). As células do tipo B, por sua vez, são caracterizadas pela presença de um retículo endoplasmático rugoso bem desenvolvido e grânulos secretórios, e são responsáveis por produzir e secretar componentes do fluido sinovial e da matriz extracelular, incluindo ácido hialurônico, colágeno e fibronectina, presentes no líquido sinovial, bem como mediadores envolvidos em processos inflamatórios como citocinas e enzimas metaloproteinases de matriz (Iwanaga et al, 2000;Sieghart et al, 2015). O líquido sinovial consiste em um dialisado de plasma sanguíneo com grandes quantidades de ácido hialurônico e glicosaminoglicanos com viscosidade suficiente para manter lubrificadas as superfícies articulares.…”

“…Neste sentido, as células sinoviais semelhantes a fibroblastos (FLS) desempenham um papel fundamental na progressão da inflamação na ATM devido a sua capacidade de produzir um grande número de mediadores inflamatórios (Kardel et al, 2003;Satoh et al, 2009;Sieghart et al, 2015).…”

Sulphur bath int he treatment of musculosceletal disorders

“…In their study, Sieghart et al concluded that exogenous H2S (NaHS) reduced the IL-1β-induced activation of fibroblast-like synoviocytes obtained from arthrosis patients, probably via the MAP-kinase and PI3K/Akt pathways [29].…”