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.

Abstract

Fibroblast growth factor (FGF)-l 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. (J. Clin. Invest. 1993. 91:553-565.)

Expression of platelet‐derived growth factors C and D in the synovial membrane of patients with rheumatoid arthritis and osteoarthritis

“…PDGF-C and PDGF-D were detected in the synovial lining layer, diffuse infiltrates, and stroma of the SM, according to the expression previously reported for PDGF-A and PDGF-B (13,15); this leads to the assumption that cells of these compartments are able to express all isoforms of PDGF. Double-labeling experiments with specific markers showed expression of both PDGF-C and PDGF-D by synovial fibroblasts and macrophages, which is consistent with recent findings of PDGF-C in dermal and lung fibroblasts (25) and in infiltrating inflammatory CD11bϩ cells in coxsackievirus B3-induced chronic myocarditis (26).…”

“…Synovial cells located in pannus show an invasive behavior, are of variable cell size (11), and express high levels of protooncogenes (12) and tyrosine phosphorylated proteins (13). PDGF receptor (PDGFR) ␣ and ␤ chains are detected in fibroblast-like cells in the inflamed synovial membrane (SM) (14).…”

Sphingosine 1‐phosphate/sphingosine 1‐phosphate receptor 1 signaling in rheumatoid synovium: Regulation of synovial proliferation and inflammatory gene expression

“…Positive staining was indicated by brownish deposits. Double antibody staining with anti-S1P 1 antibody and anti-COX-2 antibody was performed as previously described (32). For S1P 1 staining, the color was developed with a DAB solution including 0.04% (w/v) nickel chloride.…”

“…For each tissue specimen from the RA and OA patients, the extent and intensity of anti-SP-1P 1 staining in synovial lining cells, inflammatory mononuclear cells, and vascular endothelial cells was graded on a scale of 0-4ϩ by 2 blinded observers on 2 separate occasions, using coded slides as previously described (21,(30)(31)(32). The observer assigned the scores after assessment of the entire tissue section, such that a grade of 4ϩ indicated that staining was maximally intense throughout the specimen, while a grade of 0 indicated that staining was absent throughout the specimen.…”

The effects of the immunosuppressant rapamycin on the growth of rheumatoid arthritis (RA) synovial fibroblast

“…The synovial hyperplasia is probably due to stimulation by various growth factors, such as IL-1, fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) [4][5][6][7]. PDGF-BB is locally produced in the RA synovium and may play an important role in the pathogenesis of RA [7,8]. In the present study we examined the PDGF-mediated intracellular signal transduction in synovial cell growth.…”