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J Lipid Res. 2015 Jan;56(1):38-50. doi: 10.1194/jlr.M052670. Epub 2014 Oct 19.

Regulation of NF-κB signaling by oxidized glycerophospholipid and IL-1β induced miRs-21-3p and -27a-5p in human aortic endothelial cells.

Author information

1
Departments of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095.
2
Medicine, University of California, Los Angeles, Los Angeles, CA 90095.
3
Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095.
4
Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095.
5
Departments of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095 Medicine, University of California, Los Angeles, Los Angeles, CA 90095 Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095.
6
Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095.

Abstract

Exposure of endothelial cells (ECs) to agents such as oxidized glycerophospholipids (oxGPs) and cytokines, known to accumulate in atherosclerotic lesions, perturbs the expression of hundreds of genes in ECs involved in inflammatory and other biological processes. We hypothesized that microRNAs (miRNAs) are involved in regulating the inflammatory response in human aortic endothelial cells (HAECs) in response to oxGPs and interleukin 1β (IL-1β). Using next-generation sequencing and RT-quantitative PCR, we characterized the profile of expressed miRNAs in HAECs pre- and postexposure to oxGPs. Using this data, we identified miR-21-3p and miR-27a-5p to be induced 3- to 4-fold in response to oxGP and IL-1β treatment compared with control treatment. Transient overexpression of miR-21-3p and miR-27a-5p resulted in the downregulation of 1,253 genes with 922 genes overlapping between the two miRNAs. Gene Ontology functional enrichment analysis predicted that the two miRNAs were involved in the regulation of nuclear factor κB (NF-κB) signaling. Overexpression of these two miRNAs leads to changes in p65 nuclear translocation. Using 3' untranslated region luciferase assay, we identified 20 genes within the NF-κB signaling cascade as putative targets of miRs-21-3p and -27a-5p, implicating these two miRNAs as modulators of NF-κB signaling in ECs.

KEYWORDS:

cell signaling; cytokines; gene expression; inflammation oxidized lipids; interleukin 1β; microRNAs; nuclear factor κB

PMID:
25327529
PMCID:
PMC4274069
DOI:
10.1194/jlr.M052670
[Indexed for MEDLINE]
Free PMC Article

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