p65
p65
PU.1
Mir146
Mus musculus
Apolipoprotein E (ApoE) enhances purine-rich PU-box-binding protein 1 (PU.1)-dependent miR-146a transcription to suppress nuclear factor-κB (NF-κB)-driven monocyte and macrophage activation and thereby inflammation and atherosclerosis.
Environmental ligands of toll-like receptors (TLRs), including lipopolysaccharide (LPS) and oxidized low-density lipoprotein (oxLDL), caused by hyperlipidemia provoke inflammatory signaling in monocytes and macrophages resulting in NF-κB activation. Gene transcription from NF-κB activity results in the production of inflammatory mediators, including proatherogenic cytokines. It also results in the production of primary miR-146a (pri-miR-146a) that is subsequently processed into mature miR-146a that silences the expression of key TLR-adaptor molecules interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6). The production of miR-146a thereby serves as a regulatory feedback loop to suppress NF-κB activity and resolve inflammation. Findings from our study identified that cellular apoE expression contributes to amplify this regulatory feedback loop by increasing PU.1-dependent transcription of pri-miR-146a and thereby mature miR-146a production.
(WikiPathways-description)
ApoE and miR-146 in inflammation and atherosclerosis
ENSMUSG00000031392
Ensembl
ENSMUSG00000002985
Ensembl
CHEBI:16412
ChEBI
ENSMUSG00000039005
Ensembl
ENSMUSG00000024927
Ensembl
Lipopolysaccharide
ENSMUSG00000017386
Ensembl
Tlr4
Irak1
CHEBI:60151
ChEBI
20375
Entrez Gene
MI0000170
miRBase Sequence
Nfkb2
Traf4
ENSMUSG00000025225
Ensembl
ENSMUSG00000027995
Ensembl
Nfkb2
ox-LDL
ApoE
Tlr2