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Coexpression of phosphotyrosine-containing proteins, platelet-derived growth factor-B, and fibroblast growth factor-1 in situ in synovial tissues of patients with rheumatoid arthritis and Lewis rats with adjuvant or streptococcal cell wall arthritis.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 1993 Feb; Vol. 91 (2), pp. 553-65. - Publication Year :
- 1993
-
Abstract
- Fibroblast growth factor (FGF)-1 and PDGF-B-like factors have been implicated in the pathobiology of RA and animal models of this disease. Since the receptors for FGF-1 and PDGF are tyrosine kinases, we examined the expression of tyrosine phosphorylated proteins (phosphotyrosine, P-Tyr) in synovial tissues from patients with RA and osteoarthritis (OA), and rats with streptococcal cell wall (SCW) and adjuvant arthritis (AA). Synovia from patients with RA and LEW/N rats with SCW and AA arthritis, in contrast to controls, stained intensely with anti-P-Tyr antibody. The staining colocalized with PDGF-B and FGF-1 staining. Comparative immunoblot analysis showed markedly enhanced expression of a 45-kD P-Tyr protein in the inflamed synovia. Treatment with physiological concentrations of dexamethasone suppressed both arthritis and P-Tyr expression in AA. P-Tyr was only transiently expressed in athymic nude Lewis rats and was not detected in relatively arthritis-resistant F344/N rats. These data suggest that (a) FGF-1 and PDGF-B-like factors are upregulated and may induce tyrosine phosphorylation of proteins in vivo in inflammatory joint diseases, (b) persistent high level P-Tyr expression is T lymphocyte dependent, correlates with disease severity, and is strain dependent in rats, (c) corticosteroids, in physiological concentrations, downregulate P-Tyr expression in these lesions.
- Subjects :
- Animals
Female
Fibroblast Growth Factor 1 immunology
Glucocorticoids pharmacology
Humans
Immunohistochemistry
Phosphotyrosine
Platelet-Derived Growth Factor immunology
Rats
Rats, Inbred F344
Rats, Inbred Lew
Synovial Membrane chemistry
Tyrosine analysis
Tyrosine immunology
Arthritis, Experimental metabolism
Arthritis, Infectious metabolism
Arthritis, Rheumatoid metabolism
Fibroblast Growth Factor 1 analysis
Platelet-Derived Growth Factor analysis
Tyrosine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 91
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 7679410
- Full Text :
- https://doi.org/10.1172/JCI116235