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

ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder, primarily affecting the articular structures and synovial membranes of multiple joints. Beside pharmacologically based treatments, sulphur bath therapy has long been used as a therapy for patients suffering from different rheumatic disorders. But scientific reports about the beneficial effects of H2S as well as about the underlying molecular mechanisms are controversial and rare.MethodsFibroblast-like synoviocytes (FLS) derived from RA and OA-patients were treated with the H2S-donor sodium hydrogen sulphide (NaHS). IL-6 release was quantified by enzyme-linked immunosorbent assay (ELISA). Gene expression of IL-6, IL-8 and COX-2 as well as of the matrix metalloproteinases (MMPs) MMP-2, MMP-3 and MMP-14 was monitored by quantitative real-time PCR (qRT-PCR). Modulation of the mitogen-activated protein kinases (MAPKs) p38 and ERK1/2 was analysed by Western blotting.ResultsHigh concentrations of H2S (above 0.5 mM) elevated the expression of pro-inflammatory genes in RA- and OA-FLS. This was accompanied by activation of p38 and ERK1/2 MAPK. H2S-induced expression of IL-6, IL-8 and COX-2 was completely blocked by specific inhibitors of p38 and ERK1/2 MAPK and NF-κB.ConclusionH2S is a potent gaseous molecule that can upregulate the expression of a series of pro-inflammatory genes in RA and OA-FLS. Therefore, caution is advised in patients with active RA when taking sulphur bath therapy.

► Rheumatoid arthritis/osteoarthritis.
► Fibroblast-like synoviocytes.
► IL-6, IL-8, COX-2, matrix-metalloproteinases.
► Pro-inflammatory properties of H2S.
► Mitogen-activated protein kinases; Heat shock proteins.