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J Biol Chem. 2011 Jul 22;286(29):25531-9. doi: 10.1074/jbc.M111.256206. Epub 2011 May 31.

Toll-like receptor-4 (TLR4) down-regulates microRNA-107, increasing macrophage adhesion via cyclin-dependent kinase 6.

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  • 1School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.

Abstract

Toll-like receptors (TLRs) modulate the expression of multiple microRNAs (miRNAs). Here, we report the down-regulation of miR-107 by TLR4 in multiple cell types. The miR-107 sequence occurs in an intron within the sequence encoding the gene for pantothenate kinase 1α (PanK1α), which is regulated by the transcription factor peroxisome proliferator-activating receptor α (PPAR-α). PanK1α is also decreased in response to lipopolysaccharide (LPS). The effect on both miR-107 and PanK1α is consistent with a decrease in PPAR-α expression. We have found that the putative miR-107 target cyclin-dependent kinase 6 (CDK6) expression is increased by TLR4 as a result of the decrease in miR-107. This effect is required for increased adhesion of macrophages in response to LPS, and CDK6-deficient mice are resistant to the lethal effect of LPS. We have therefore identified a mechanism for LPS signaling which involves a decrease in miR-107 leading to an increase in CDK6.

PMID:
21628465
[PubMed - indexed for MEDLINE]
PMCID:
PMC3138295
Free PMC Article

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