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 [4], 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.

References

1. Fernandes, JC, J Martel-Pelletier, and JP Pelletier, The role of cytokines in osteoarthritis pathophysiology. Biorheology, 2002. 39(1-2): p. 237-46.

2. Roman-Blas, JA, DG Stokes, and SA Jimenez, Modulation of TGF-beta signaling by proinflammatory cytokines in articular chondrocytes. Osteoarthritis Cartilage, 2007. 15(12): p. 1367-77.

3. Smith, MD, S Triantafillou, A Parker, et al., Synovial membrane inflammation and cytokine production in patients with early osteoarthritis. J Rheumatol, 1997. 24(2): p. 365-71.

4. Francon, A and R Forestier, [Spa therapy in rheumatology. Indications based on the clinical guidelines of the French National Authority for health and the European League Against Rheumatism, and the results of 19 randomized clinical trials]. Bull Acad Natl Med, 2009. 193(6): p. 1345-56.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.3609