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

J Clin Invest. 1993 Feb;91(2):553-65. doi: 10.1172/JCI116235.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arthritis, Experimental / metabolism*
  • Arthritis, Infectious / metabolism*
  • Arthritis, Rheumatoid / metabolism*
  • Female
  • Fibroblast Growth Factor 1 / analysis*
  • Fibroblast Growth Factor 1 / immunology
  • Glucocorticoids / pharmacology
  • Humans
  • Immunohistochemistry
  • Phosphotyrosine
  • Platelet-Derived Growth Factor / analysis*
  • Platelet-Derived Growth Factor / immunology
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Synovial Membrane / chemistry
  • Tyrosine / analogs & derivatives*
  • Tyrosine / analysis
  • Tyrosine / immunology

Substances

  • Glucocorticoids
  • Platelet-Derived Growth Factor
  • Fibroblast Growth Factor 1
  • Phosphotyrosine
  • Tyrosine