A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations

Irvine, Katharine M., Burns, Christopher J., Wilks, Andrew F., Su, Stephen, Hume, David A. and Sweet, Matthew J. (2006) A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations. The FASEB Journal, 20 11: 1921-1923. doi:10.1096/fj.06-5848fje


Author Irvine, Katharine M.
Burns, Christopher J.
Wilks, Andrew F.
Su, Stephen
Hume, David A.
Sweet, Matthew J.
Title A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
1530-6860
Publication date 2006-09-01
Sub-type Article (original research)
DOI 10.1096/fj.06-5848fje
Open Access Status Not Open Access
Volume 20
Issue 11
Start page 1921
End page 1923
Total pages 3
Place of publication Bethesda, MD, United States
Publisher Federation American Society of Experimental Biology
Language eng
Formatted abstract
CSF-1 regulates macrophage differentiation, survival, and function, and is an attractive therapeutic target for chronic inflammation and malignant diseases. Here we describe the effects of a potent and selective inhibitor of CSF-1R -CYC10268 -on CSF1R-dependent signaling. In in vitro kinase assays, CYC10268 was active in the low nanomolar range and showed selectivity over other kinases such as Ab1 and Kit. CYC10268 blocked survival mediated by CSF-1R in primary murine bone marrow-derived macrophages (BMM) and in the factor-dependent cell line Ba/ F3, in which the CSF-1R was ectopically expressed. CYC10268 also inhibited CSF-1 regulated signaling (Akt, ERK-1/ 2), gene expression (urokinase plasminogen activator, toll-like receptor 9, and apolipoprotein E), and priming of LPS-inducible cytokine production in BMM. In thioglycollate-elicited peritoneal macrophages (TEPM), which survive in the absence of exogenous CSF-1, CYC10268 impaired LPS-induced cytokine production and regulated expression of known CSF-1 target genes. These observations support the conclusion that TEPM are CSF-1 autocrine and that CSF-1 plays a central role in macrophage effector functions during inflammation. CSF-1R inhibitors such as CYC10268 provide a powerful tool to dissect the role of the CSF-1/ CSF-1R signaling system in a range of biological systems and have potential for a number of therapeutic applications.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 19:40:46 EST