The role of MicroRNAs miR-200b and miR-200c in TLR4 signaling and NF-κB activation

Erik B Wendlandt; Joel W Graff; Theresa L Gioannini; Anton P McCaffrey; Mary E Wilson

doi:10.1177/1753425912443903

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The role of MicroRNAs miR-200b and miR-200c in TLR4 signaling and NF-κB activation

Journal article

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The role of MicroRNAs miR-200b and miR-200c in TLR4 signaling and NF-κB activation

Erik B Wendlandt, Joel W Graff, Theresa L Gioannini, Anton P McCaffrey and Mary E Wilson

Innate immunity (London, England), Vol.18(6), pp.846-855

12/2012

DOI: 10.1177/1753425912443903

PMCID: PMC3733339

PMID: 22522429

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Abstract

Recognition of microbial products by members of the Toll-like receptor (TLR) family initiates intracellular signaling cascades that result in NF-κB activation and subsequent production of inflammatory cytokines. We explored the potential roles of microRNAs (miRNAs) in regulating TLR pathways. A target analysis approach to the TLR4 pathway adaptor molecules identified several putative targets of miR-200a, miR-200b and miR-200c. miRNA mimics were co-transfected with a NF-κB activity reporter plasmid into HEK293 cells stably expressing TLR4 (HEK293-TLR4). Mimics of both miR-200b and miR-200c, but not miR-200a, decreased NF-κB reporter activity in either untreated cells or in cells treated with endotoxin:MD2 as a TLR4 agonist. Transfection of HEK293-TLR4 cells with miR-200b or miR-200c significantly decreased expression of MyD88, whereas TLR4, IRAK-1 and TRAF-6 mRNAs were unaffected. When miR-200b or miR-200c mimics were transfected into the differentiated monocytic THP-1 cell line, the abundance of MyD88 transcripts, as well as LPS-induced expression of the pro-inflammatory molecules IL-6, CXCL9 and TNF-α were diminished. These data define miRNAs miR-200b and miR-200c as factors that modify the efficiency of TLR4 signaling through the MyD88-dependent pathway and can thus affect host innate defenses against microbial pathogens.

microRNAs

pro-inflammatory response

Toll-like receptor

gene expression

Macrophage

Details

Title: Subtitle: The role of MicroRNAs miR-200b and miR-200c in TLR4 signaling and NF-κB activation
Creators: Erik B Wendlandt - Department of Epidemiology, University of Iowa, IA, USA
Joel W Graff - Department of Epidemiology, University of Iowa, IA, USA
Theresa L Gioannini - Department of Epidemiology, University of Iowa, IA, USA
Anton P McCaffrey - Department of Epidemiology, University of Iowa, IA, USA
Mary E Wilson - Department of Epidemiology, University of Iowa, IA, USA
Resource Type: Journal article
Publication Details: Innate immunity (London, England), Vol.18(6), pp.846-855
DOI: 10.1177/1753425912443903
PMID: 22522429
PMCID: PMC3733339
ISSN: 1753-4259
eISSN: 1753-4267
Grant note: R01 AI076233 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI045540 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI067874 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID T32 AI007511 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R21 AI080801 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
Language: English
Date published: 12/2012
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Internal Medicine
Record Identifier: 9984001137102771

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