Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages

Irvine, Katharine M., Andrews, Melanie R., Fernandez-Rojo, Manuel A., Schroder, Kate, Burns, Christopher J., Su, Stephen, Wilks, Andrew F., Parton, Robert G., Hume, David A. and Sweet, Matthew J. (2009) Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages. Journal of Leukocyte Biology, 85 2: 278-288. doi:10.1189/jlb.0808497


Author Irvine, Katharine M.
Andrews, Melanie R.
Fernandez-Rojo, Manuel A.
Schroder, Kate
Burns, Christopher J.
Su, Stephen
Wilks, Andrew F.
Parton, Robert G.
Hume, David A.
Sweet, Matthew J.
Title Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages
Journal name Journal of Leukocyte Biology   Check publisher's open access policy
ISSN 0741-5400
Publication date 2009-02
Year available 2008
Sub-type Article (original research)
DOI 10.1189/jlb.0808497
Volume 85
Issue 2
Start page 278
End page 288
Total pages 11
Place of publication Bethesda
Publisher Federation American Society of Experimental Biology
Collection year 2009
Language eng
Subject 320202 Cellular Immunology
730102 Immune system and allergy
C1
06 Biological Sciences
0601 Biochemistry and Cell Biology
Abstract M-CSF/CSF-1 supports the proliferation and differentiation of monocytes and macrophages. In mice, CSF-1 also promotes proinflammatory responses in vivo by regulating mature macrophage functions, but little is known about the acute effects of this growth factor on mature human macrophages. Here, we show that in contrast to its effects on mouse bone marrow-derived macrophages, CSF-1 did not induce expression of urokinase plasminogen activator mRNA, repress expression of apolipoprotein E mRNA, or prime LPS-induced TNF and IL-6 secretion in human monocyte-derived macrophages (HMDM) from several independent donors. Instead, we show by expression profiling that CSF-1 modulates the HMDM transcriptome to favor a proatherogenic environment. CSF-1 induced expression of the proatherogenic chemokines CXCL10/IFN-inducible protein 10, CCL2, and CCL7 but repressed expression of the antiatherogenic chemokine receptor CXCR4. CSF-1 also up-regulated genes encoding enzymes of the cholesterol biosynthetic pathway (HMGCR, MVD, IDI1, FDPS, SQLE, CYP51A1, EBP, NSDHL, DHCR7, and DHCR24), and expression of ABCG1, encoding a cholesterol efflux transporter, was repressed. Consistent with these effects, CSF-1 increased levels of free cholesterol in HMDM, and the selective CSF-1R kinase inhibitor GW2580 ablated this response. These data demonstrate that CSF-1 represents a further link between inflammation and cardiovascular disease and suggest two distinct mechanisms by which CSF-1, which is known to be present in atherosclerotic lesions, may contribute to plaque progression.
Keyword Chemokines
Cholesterol
Inflammation
Q-Index Code C1
Q-Index Status Confirmed Code
Additional Notes Published online before print November 12, 2008

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Institute for Molecular Bioscience - Publications
 
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Created: Thu, 19 Feb 2009, 16:33:02 EST by Cody Mudgway on behalf of Institute for Molecular Bioscience