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).

CONCLUSION

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.