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.
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.
Sano
H
H
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Disease, National Institutes of Health, Bethesda, Maryland 20892.
Engleka
K
K
Mathern
P
P
Hla
T
T
Crofford
L J
LJ
Remmers
E F
EF
Jelsema
C L
CL
Goldmuntz
E
E
Maciag
T
T
Wilder
R L
RL
D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001170:Arthritis, Infectious / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000032:analysis* / Q000276:immunology; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D019000:Phosphotyrosine; D010982:Platelet-Derived Growth Factor / Q000032:analysis* / Q000276:immunology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D013583:Synovial Membrane / Q000737:chemistry; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000276:immunology
D005938:Glucocorticoids; D010982:Platelet-Derived Growth Factor; D016220:Fibroblast Growth Factor 1; D019000:Phosphotyrosine; D014443:Tyrosine