Manns, Joanne M.;
Uknis, Audrey B.;
Rico, Mario C.;
Agelan, Alexis;
Castaneda, Julian;
Arango, Israel;
Barbe, Mary F.;
Safadi, Fayez F.;
Popoff, Steven N.;
DeLa Cadena, Raul A.
A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor
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Media type:
E-Article
Title:
A peptide from thrombospondin 1 modulates experimental erosive arthritis by regulating connective tissue growth factor
Contributor:
Manns, Joanne M.;
Uknis, Audrey B.;
Rico, Mario C.;
Agelan, Alexis;
Castaneda, Julian;
Arango, Israel;
Barbe, Mary F.;
Safadi, Fayez F.;
Popoff, Steven N.;
DeLa Cadena, Raul A.
Published:
Wiley, 2006
Published in:
Arthritis & Rheumatism, 54 (2006) 8, Seite 2415-2422
Description:
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with leukocyte adhesion to and extravasation through vascular endothelium into synovial tissue. Recent evidence indicates that the thrombospondin 1 gene is up‐regulated in patients with RA. We have identified a region within the TSP‐1 type 3 repeats that inhibits human neutrophil elastase (HNE) and binds to human neutrophils. The present study was undertaken to investigate the therapeutic benefit of this TSP‐1–derived peptide sequence and its effect on connective tissue growth factor (CTGF), a protein involved in fibrotic disorders and in neovascularization, which is a hallmark of RA.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>CTGF gene and protein expression, as well as protein levels of CTGF in the synovium, after treatment with the TSP‐1–derived peptide were studied in the peptidoglycan–polysaccharide animal model of erosive arthritis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Peptide treatment prevented joint infiltration and inflammation and was associated with reduced circulating antigen levels of HNE and TSP‐1. Additionally, CTGF was up‐regulated in this experimental model of RA. Treatment with the TSP‐1–derived peptide was associated with down‐regulation of the message and protein levels of CTGF. Immunofluorescence studies showed that the mean area fraction of CTGF immunoreactivity in the peptide‐treated group of animals was significantly less than that in the untreated group.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>These results document a role for TSP‐1 in regulating CTGF gene and protein expression in synovial tissue, suggesting a link with the disease course in this model of RA. This TSP‐1–derived synthetic peptide may represent an important template for drug development in RA and other inflammatory conditions associated with neutrophil activation.</jats:p></jats:sec>