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Pro- and anti-inflammatory control of M-CSF-mediated macrophage differentiation

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 investiga...

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Main Authors: Popova, Anna (Author) , Kzhyshkowska, Julia (Author) , Nurgazieva, Dinara (Author) , Goerdt, Sergij (Author) , Gratchev, Alexei (Author)
Format: Article (Journal)
Language:English
Published: 2011
In: Immunobiology
Year: 2011, Volume: 216, Issue: 1-2, Pages: 164-172
ISSN:1878-3279
DOI:10.1016/j.imbio.2010.06.003
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.imbio.2010.06.003
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Author Notes:Anna Popova, Julia Kzhyshkowska, Dinara Nurgazieva, Sergij Goerdt, Alexei Gratchev

MARC

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520 |a 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 Th1 and Th2 cytokines (IFN-γ and IL-4) and tolerogenic stimuli - glucocorticoid dexamethasone in primary human monocyte derived macrophages. We show that IFN-γ 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 Th1 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. 
650 4 |a Cell Culture Techniques 
650 4 |a Cell Differentiation 
650 4 |a Cell Separation 
650 4 |a Cells, Cultured 
650 4 |a Cytokines 
650 4 |a Dexamethasone 
650 4 |a Flow Cytometry 
650 4 |a Gene Expression Regulation 
650 4 |a Humans 
650 4 |a Immune Tolerance 
650 4 |a Inflammation 
650 4 |a Macrophage Colony-Stimulating Factor 
650 4 |a Macrophages 
650 4 |a Receptor, Macrophage Colony-Stimulating Factor 
650 4 |a Th1-Th2 Balance 
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