Journal
IMMUNOBIOLOGY
Volume 216, Issue 1-2, Pages 164-172Publisher
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2010.06.003
Keywords
Differentiation; Glucocorticoid; IFN-gamma; IL-4; Inflammation; Macrophage
Categories
Funding
- Deutsche Forschungsgemeinschaft [SFB405, B12]
- Margarete von Wrangell Habilitationsprogramm
- Russian Foundation for Basic Research [09-04-01752-a]
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Macrophages play a key role in inflammation, tissue regeneration and tolerance. Their differentiation is regulated by tissue cells derived CSF-1 (M-CSF). The ability of macrophages to use autocrine M-CSF to control their differentiation and function remained controversial. In this study we investigated the regulation of M-CSF production by Thl and Th2 cytokines (IFN-gamma and IL-4) and tolerogenic stimuli glucocorticoid dexamethasone in primary human monocyte derived macrophages. We show that IFN-gamma and IL-4 efficiently induce production of M-CSF while glucocorticoid inhibited it in a dose dependent manner. Since glucocorticoid inhibits production of inflammatory cytokines we tested whether this effect is a result of inhibited M-CSF production. We showed that exogenous M-CSF rescues the ability of glucocorticoid-treated macrophages to produce TNF and IL-6 in response to LPS. These data indicate that glucocorticoid-treated macrophages retain the ability to respond to M-CSF. Analyzing the mechanism of this responsiveness, we showed that dexamethasone up-regulates surface expression of M-CSF receptor -CSF-1R. We conclude that the ability of macrophages to produce M-CSF secures macrophage differentiation under Thl and Th2 conditions if tissue cells are unable to supply enough M-CSF. Increased surface expression of CSF-1R in tolerogenic conditions guarantees response to minute amounts of exogenous M-CSF. (C) 2010 Elsevier GmbH. All rights reserved.
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