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UBC Theses and Dissertations

Pro-inflammatory platelet factor 4 (CXCL4/PF4) signaling in rheumatoid arthritis To, Jeffrey


Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joint tissues caused by activation of locally recruited immune cells. Within the joints, the resident fibroblast-like synoviocytes (FLS) play an important role in RAassociated tissue degradation in part due to their secretion of pro-inflammatory cytokines and tissue-degrading matrix metalloproteinases (MMPs) into the synovium, as well as the cells’ ability to invade nearby structures. Platelets also function as immune cells that contain and secrete pro-inflammatory molecules but their role in RA is not understood. Of particular interest is platelet factor 4 (PF4), a major constituent of platelet alpha-granules. Methods: Cultured SW982 cells were used as a model for FLS. Cells were cultured in the presence or absence of recombinant PF4. The secretion of MMP-1 (interstitial collagenase) was measured by enzyme-linked immunosorbent assay (ELISA). Cell adhesion was determined by wash-off assays. Results: Cells cultured with recombinant PF4 secreted more MMP-1 relative to controls. PF4 treatment also increased the FLS production of fibronectin, a matrix adhesion molecule. PF4- treated cells also exhibited greater adhesion and spreading. Conclusion: I conclude that PF4 contributes to an invasive/destructive phenotype in FLS, by promoting MMP-1 release and increased cell adhesion.

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