Regulation of synovial cell growth: basic fibroblast growth factor synergizes with interleukin 1 beta stimulating phospholipase A2 enzyme activity, phospholipase A2 activating protein production and release of prostaglandin E2 by rheumatoid arthritis synovial cells in culture.
Cytokines have been implicated in the regulation of eicosanoid synthesis and synovial cell proliferation. To further define these mechanisms, we have compared the effects of basic fibroblast growth factor and platelet-derived growth factor on cell growth, prostaglandin E2 (PGE2) production and phospholipase A2 enzyme activity in long-term cultures of synovial cells from rheumatoid arthritis (RA) patients capable of proliferating in serum-free medium. Compared with serum-free medium alone, RA synovial cell growth was significantly enhanced by adding either basic fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF) to the culture medium. Growing RA synovial cells for 14 days in serum-free medium plus bFGF caused them to spontaneously release significant amounts of PGE2, an effect not seen if cells were grown in serum-free medium alone, or serum-free medium plus PDGF. Enhanced release of PGE2 occurred when arachidonic acid was added to bFGF but not PDGF-treated RA synovial cells, suggesting that bFGF increased cyclooxygenase enzyme activity in these cells. Moreover, phospholipase A2 (PLA2) enzyme activity was found to be significantly greater in RA synovial cells grown for 14 days in serum-free medium containing bFGF alone, or bFGF plus interleukin 1 beta (IL-1 beta) compared with cells grown in either serum-free medium alone, or serum-free medium plus PDGF. Similarly, bFGF plus IL-1 beta-stimulated release of PLA2 activating protein, a novel mammalian phospholipase stimulator found in high concentrations in RA synovial fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
Goddard
D H
DH
Department of Medicine, Winthrop-University Hospital, Mineola, NY 11501.
Grossman
S L
SL
Newton
R
R
Clark
M A
MA
Bomalaski
J S
JS
D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000008:administration & dosage*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology*
D007375:Interleukin-1; D010982:Platelet-Derived Growth Factor; D011506:Proteins; C055324:phospholipase A2-activating protein; D016222:Fibroblast Growth Factor 2; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone