Background In the pathophysiology of osteoarthritis (OA) the secretion of pro-inflammatory cytokine interleukin (IL)-1β is among the critical steps mediating aberrant degenerative processes in which activated fibroblast-like synoviocytes (FLS) play a pivotal role [1-3].
Objectives Since hydrogen sulfide (H2S) seems to positively manipulate cells that are affected during degenerative joint disease , it was the objective of this study to investigate the effects of exogenous H2S on IL-1β-activated FLS.
Methods Primary cell lines derived from FLS of patients with OA were used throughout this study. The effects of IL-1β and NaHS treatment on the phosphorylation of MAP kinases were analyzed by proteome profiler array covering 26 different kinases. The secretion of IL-6 was monitored by ELISA in cell culture supernatants from cultured FLS treated with NaHS. In addition, FLS were grown in 3-dimensional extracellular matrix micromass cultures, stimulated with IL-1β and treated with NaHS.
Results NaHS treatment significantly reduced spontaneous and IL-1β-induced IL-6 production. Data from human phospho-MAPK proteome profiler array revealed that IL-1β upregulated the phosphorylation of several MAPkinases but decreased the amount of p-Akt. Remarkably, NaHS treatment inhibited the IL-1β-induced activation of MAPkinases and induced the phosphorylation of Akt. FLS micromass cultures stimulated with IL-1β developed a hyperplastic lining layer-like structure and treatment with NaHS almost completely inhibited this process.
Conclusions Our results propose anti-inflammatory properties of hydrogen sulfide on activated synovial fibroblasts that result from selective manipulation of the MAPkinase and the PI3K/Akt pathway.
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Disclosure of Interest None declared