Rheumatoid arthritis synovial tissue fibroblast Mucin 3 expression and function (54.27)

Abstract

Abstract Mucin 3 (MUC3) is elevated in rheumatoid arthritis (RA) synovial tissues (STs). We hypothesized that MUC3 is expressed by RA synovial fibroblasts, that it is cytokine inducible and chemotactic for RA synovial fibroblasts. To test this, RA synovial fibroblast MUC3 expression was determined by immunohistochemistry, flow cytometry and Western blot analysis. Levels of MUC3 from arthritic synovial fluids (SFs) were measured by a novel MUC3 ELISA. RA synovial fibroblast chemotaxis to RA SFs was assessed using a modified Boyden chamber assay. RA ST cells stained for both MUC3 and vimentin indicating that RA synovial fibroblasts express MUC3. Flow cytometry experiments showed that most of the RA synovial fibroblast MUC3 is cytoplasmic. Cytokine stimulation of these cells significantly increased MUC3 production (P<0.05). RA SFs contain on average 8.7μg/ml (n=8) of MUC3. Immunodepletion of MUC3 from RA SFs resulted in significantly reduced RA synovial fibroblast chemotaxis (P<0.05, n=5 RA SFs and n=8 RA synovial fibroblasts). These results show that MUC3 is produced by synovial fibroblasts in RA STs, that MUC3 is inducible by cytokine stimulation and that RA SF induced synovial fibroblast chemotaxis can be inhibited by depleting MUC3. Thus, MUC3 synovial fibroblast production may be induced by the inflammatory milieu of the RA joint and may drive synovial fibroblast chemotaxis within the RA ST potentially aiding pannus formation and cartilage destruction.