p65 p65 PU.1 Mir146 Mus musculus ApoE and miR-146 in inflammation and atherosclerosis 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) ENSMUSG00000025225 Ensembl ENSMUSG00000024927 Ensembl CHEBI:16412 ChEBI MI0000170 miRBase Sequence 20375 Entrez Gene Lipopolysaccharide ENSMUSG00000002985 Ensembl Tlr4 Irak1 CHEBI:60151 ChEBI ENSMUSG00000027995 Ensembl ENSMUSG00000027164 Ensembl Nfkb2 ENSMUSG00000039005 Ensembl Traf6 ENSMUSG00000031392 Ensembl Nfkb2 ox-LDL ApoE Tlr2