Cytokines and growth regulation of synoviocytes from patients with rheumatoid arthritis and rats with streptococcal cell wall arthritis.
Paracrine growth factors probably stimulate the pathologic proliferation of synovial fibroblast-like cells (synoviocytes) in rheumatoid arthritis (RA), but the relative importance of various factors is highly controversial. To address this problem, we compared the effects of highly purified or recombinant cytokines, in serum-free medium, on the in vitro long-term growth of synoviocytes from patients with RA and rats with streptococcal cell wall (SCW) arthritis. Of the factors tested (PDGF, aFGF, bFGF, EGF, TGF-beta, IL-1-alpha, TNF-alpha and IFN-gamma), PDGF, was clearly the most potent stimulant of long-term growth of both rat and human synoviocytes. The strong mitogenic activity of rheumatoid synovial fluids was significantly inhibited by neutralizing anti-PDGF antibody, thus confirming the importance of PDGF. EGF, TGF-beta, IL-1-alpha, TNF-alpha, and IFN-gamma had minimal effects. Similar to the effects on anchorage-independent growth, TGF-beta 1 and 2, inhibited serum- or PDGF-stimulated anchorage-dependent growth. Considered in the context of other reports, these data support the view that cytokines such as PDGF, and possibly aFGF and bFGF, play major roles in stimulating synoviocyte hyperplasia in RA and SCW arthritis, whereas TGF-beta may inhibit synoviocyte growth.
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892.
E F
EF
Remmers
R
R
Lafyatis
G K
GK
Kumkumian
J P
JP
Case
A B
AB
Roberts
M B
MB
Sporn
R L
RL
Wilder
D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001685:Biological Factors / Q000494:pharmacology* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002473:Cell Wall; D016207:Cytokines; D005260:Female; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D051381:Rats; D011917:Rats, Inbred Lew; D013291:Streptococcus; D013582:Synovial Fluid / Q000502:physiology; D013583:Synovial Membrane / Q000473:pathology*; D015291:Transforming Growth Factors / Q000494:pharmacology
D001685:Biological Factors; D016207:Cytokines; D006133:Growth Substances; D015291:Transforming Growth Factors