Regulation of macrophage colony-stimulating factor (M-CSF) production in cultured human synovial fibroblasts.
OBJECTIVE
To study the regulation of macrophage-colony stimulating factor (M-CSF) formation in vitro by human synovial fibroblast-like cells.


METHODS
Human synovial cell explant cultures were established using cells from non-rheumatoid donors. M-CSF antigen was measured by immunoassay, and messenger RNA (mRNA) levels were determined by Northern blot.


RESULTS
The cytokines, interleukin-1 (IL-1), tumor necrosis factor alpha (TNF alpha), interferon-gamma (IFN-gamma) and IL-4, increased production of M-CSF above constitutive levels. The presence of the cyclooxygenase inhibitor, indomethacin, potentiated the action of IL-1 on M-CSF synthesis, suggesting that an endogenous cyclooxygenase product(s) can down-regulate M-CSF formation. Changes in M-CSF mRNA levels paralleled those in protein levels. The glucocorticoid, dexamethasone, and the retinoid, all-trans retinoic acid, stimulated M-CSF formation. The control of M-CSF synthesis in the synovial fibroblasts differs from that for granulocyte macrophage-CSF (GM-CSF) and granulocyte-CSF (G-CSF).


CONCLUSIONS
These results suggest that cytokine-stimulated synovial fibroblasts may be a source of M-CSF production in the joints of patients with inflammatory arthritis; as a result, monocyte/macrophages may be activated, leading to perpetuation of the inflammation and destructive events occurring in these lesions.
Hamilton
J A
JA
University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Australia.
Filonzi
E L
EL
Ianches
G
G
D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D003907:Dexamethasone; D016173:Macrophage Colony-Stimulating Factor; D007213:Indomethacin