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.

Sano H, Engleka K, Mathern P, Hla T, Crofford LJ, Remmers EF, Jelsema CL, Goldmuntz E, Maciag T, Wilder RL
J Clin Invest. 1993 91 (2): 553-65

PMID: 7679410 · PMCID: PMC287978 · DOI:10.1172/JCI116235

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.

MeSH Terms (16)

Animals Arthritis, Experimental Arthritis, Infectious Arthritis, Rheumatoid Female Fibroblast Growth Factor 1 Glucocorticoids Humans Immunohistochemistry Phosphotyrosine Platelet-Derived Growth Factor Rats Rats, Inbred F344 Rats, Inbred Lew Synovial Membrane Tyrosine

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