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Cytokine regulation of colony-stimulating factor (CSF) production in
cultured human synovial fibroblasts. II. Similarities and differences in
the control of interleukin-1 induction of granulocyte-macrophage CSF and
granulocyte-CSF production
JA Hamilton, DS Piccoli, J Cebon, JE Layton, P Rathanaswani, SR McColl and T Leizer
Department of Medicine, University of Melbourne, Royal Melbourne Hospital,
Parkville, Australia.
Synovial fibroblasts are likely to be a significant source of
granulocyte-macrophage colony-stimulating factor (GM-CSF) and
granulocyte-CSF (G-CSF), which could be crucial to the pathogenesis of
rheumatoid arthritis. Using specific enzyme-linked immunosorbent assays
(ELISAs) and Northern analysis, GM-CSF and G-CSF expression were followed
in human synovial fibroblast-like cells in response to a number of agents,
either alone or in the presence of an optimal stimulatory concentration of
interleukin-1 (IL-1). For both CSFs, interferon-gamma (100 U/mL) did not
increase their levels but dramatically suppressed the stimulatory action of
IL-1, while basic fibroblast growth factor (10(-8) mol/L), although
nonstimulatory by itself, potentiated IL-1 action. The glucocorticoid,
dexamethasone (10(- 7) mol/L), inhibited IL-1-stimulated CSF production.
However, evidence was obtained for noncoordinated CSF regulation.
Cyclooxygenase inhibitors potentiated the action of IL-1 on GM-CSF
synthesis but suppressed G-CSF synthesis, suggesting that endogenous
cyclooxygenase products can have opposite effects in modulating the levels
of each CSF. Also, the lymphokine, IL-4 (250 pmol/L), slightly inhibited
GM-CSF formation in the presence of IL-1 but elevated the G-CSF levels in
these cultures without having an effect by itself. Transforming growth
factor beta (less than or equal to 20 ng/mL) did not modulate levels of
either CSF. Mesenchymal cell production of both GM-CSF and G-CSF is
generally viewed as being under coordinate control; our findings suggest
that their synthesis in IL-1-stimulated human synoviocytes can be modulated
by a number of agents, in some cases with divergent actions depending on
which CSF is examined.
Volume 79,
Issue 6,
pp. 1413-1419,
03/15/1992
Copyright © 1992 by The American Society of Hematology
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