Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages

Sweet, Matthew J., Campbell, Carol C., Sester, David P., Xu, Damo, McDonald, Rebecca C., Stacey, Katryn J., Hume, David A. and Liew, Foo Y. (2002) Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages. Journal of Immunology, 168 1: 392-399.

Author Sweet, Matthew J.
Campbell, Carol C.
Sester, David P.
Xu, Damo
McDonald, Rebecca C.
Stacey, Katryn J.
Hume, David A.
Liew, Foo Y.
Title Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2002-01-01
Sub-type Article (original research)
Volume 168
Issue 1
Start page 392
End page 399
Total pages 8
Place of publication Bethesda
Publisher American Association of Immunologists
Language eng
Subject C1
270199 Biochemistry and Cell Biology not elsewhere classified
780105 Biological sciences
Abstract During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.
Keyword Immunology
Activated Protein-kinases
P40 Gene Promoter
Bacterial-dna
Mouse Macrophages
In-vivo
Cell Activation
Cutting Edge
M-csf
Endotoxin
Mice
Q-Index Code C1

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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