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Nat Commun. 2014 Jun 9;5:3979. doi: 10.1038/ncomms4979.

Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes.

Author information

1
1] CGAT Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK [2].
2
1] Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK [2].
3
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK.
4
Respiratory Research Group, University Hospital of South Manchester, University of Manchester, Southmoor Road, Manchester M23 9LY, UK.
5
Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
6
Department of Functional and Comparative Genomics, Centre for Genomic Research, University of Liverpool, Liverpool L69 3BX, UK.
7
CGAT Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK.
8
1] Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK [2] Respiratory Research Group, University Hospital of South Manchester, University of Manchester, Southmoor Road, Manchester M23 9LY, UK [3] Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.

Abstract

Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown of nuclear-localized, NF-κB-regulated, eRNAs (IL1β-eRNA) and RBT (IL1β-RBT46) surrounding the IL1β locus, attenuates LPS-induced messenger RNA transcription and release of the proinflammatory mediators, IL1β and CXCL8. We predict that lncRNAs can be important regulators of the human innate immune response.

PMID:
24909122
PMCID:
PMC4061460
DOI:
10.1038/ncomms4979
[Indexed for MEDLINE]
Free PMC Article
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