Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.

Hdl Handle:
http://hdl.handle.net/10147/87673
Title:
Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.
Authors:
Sheedy, FJ; Palsson-McDermott, E; Hennessy, EJ; Martin, C; O'Leary, J; Ruan, Q; Johnson, DP; Chen, Y; O'Neill, LA
Affiliation:
School of Biochemistry & Immunology, Trinity College, Dublin, Ireland.
Citation:
Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. 2009: Nat. Immunol.
Journal:
Nature immunology
Issue Date:
29-Nov-2009
URI:
http://hdl.handle.net/10147/87673
DOI:
10.1038/ni.1828
PubMed ID:
19946272
Abstract:
The tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 induction in cells lacking PDCD4. Treatment of human peripheral blood mononuclear cells with LPS resulted in lower PDCD4 expression, which was due to induction of the microRNA miR-21 via the adaptor MyD88 and NF-kappaB. Transfection of cells with a miR-21 precursor blocked NF-kappaB activity and promoted IL-10 production in response to LPS, whereas transfection with antisense oligonucleotides to miR-21 or targeted protection of the miR-21 site in Pdcd4 mRNA had the opposite effect. Thus, miR-21 regulates PDCD4 expression after LPS stimulation.
Item Type:
Article
Language:
en
ISSN:
1529-2916

Full metadata record

DC FieldValue Language
dc.contributor.authorSheedy, FJen
dc.contributor.authorPalsson-McDermott, Een
dc.contributor.authorHennessy, EJen
dc.contributor.authorMartin, Cen
dc.contributor.authorO'Leary, Jen
dc.contributor.authorRuan, Qen
dc.contributor.authorJohnson, DPen
dc.contributor.authorChen, Yen
dc.contributor.authorO'Neill, LAen
dc.date.accessioned2009-12-09T10:03:00Z-
dc.date.available2009-12-09T10:03:00Z-
dc.date.issued2009-11-29-
dc.identifier.citationNegative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21. 2009: Nat. Immunol.en
dc.identifier.issn1529-2916-
dc.identifier.pmid19946272-
dc.identifier.doi10.1038/ni.1828-
dc.identifier.urihttp://hdl.handle.net/10147/87673-
dc.description.abstractThe tumor suppressor PDCD4 is a proinflammatory protein that promotes activation of the transcription factor NF-kappaB and suppresses interleukin 10 (IL-10). Here we found that mice deficient in PDCD4 were protected from lipopolysaccharide (LPS)-induced death. The induction of NF-kappaB and IL-6 by LPS required PDCD4, whereas LPS enhanced IL-10 induction in cells lacking PDCD4. Treatment of human peripheral blood mononuclear cells with LPS resulted in lower PDCD4 expression, which was due to induction of the microRNA miR-21 via the adaptor MyD88 and NF-kappaB. Transfection of cells with a miR-21 precursor blocked NF-kappaB activity and promoted IL-10 production in response to LPS, whereas transfection with antisense oligonucleotides to miR-21 or targeted protection of the miR-21 site in Pdcd4 mRNA had the opposite effect. Thus, miR-21 regulates PDCD4 expression after LPS stimulation.-
dc.languageENG-
dc.language.isoenen
dc.titleNegative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.en
dc.typeArticleen
dc.contributor.departmentSchool of Biochemistry & Immunology, Trinity College, Dublin, Ireland.en
dc.identifier.journalNature immunologyen

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