Anti-inflammatory Effects of Yopm in Rheumatoid Arthritis Fibroblast-like Synoviocytes

Introduction Fibroblast-like synoviocytes (FLS) are key players in the pathogenesis of rheumatoid arthritis (RA). During the onset of the disease, they are transformed into an aggressive phenotype that sustains the joint-destructive infl ammatory environment of RA. This transformation is most likely due to the combination of cytokines, growth factors and cellular interaction, which leads to the stable activated phenotype. YopM is the outer protein M of Yersinia species. It has cell penetrating properties and can translocate into the cell by its two N-terminal α-helices. Interestingly, YopM is capable of downregulating infl ammatory response in host tissues infected with Yersinia. Based on these fi ndings – self-delivering ability and anti-infl ammatory properties – we investigated the effect of isolated recombinant YopM on RA-FLS. Material and methods We analysed the uptake of YopM into RA-FLS, using Cy3-coupled YopM and laser scanning microscopy. To analyse the effect of YopM on the infl ammation in RA we used RA-FLS of four patients and investigated the production of MMPs and IL-6 using ELISA. Cells were preincubated with TNF-α for 24 h and then simultaneously incubated with TNF-α and YopM or treated with YopM during TNF-α stimulation without preincubation.