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Pro-inflammatory platelet factor 4 (CXCL4/PF4) signaling in rheumatoid arthritis To, Jeffrey
Abstract
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.
Item Metadata
Title |
Pro-inflammatory platelet factor 4 (CXCL4/PF4) signaling in rheumatoid arthritis
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2019
|
Description |
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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Genre | |
Type | |
Language |
eng
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Date Available |
2022-09-30
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0380510
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2019-09
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivatives 4.0 International