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- Title
Negative regulation of TLR4 via targeting of the proinflammatory tumor suppressor PDCD4 by the microRNA miR-21.
- Authors
Sheedy, Frederick J; Palsson-McDermott, Eva; Hennessy, Elizabeth J; Martin, Cara; O'Leary, John J; Ruan, Qingguo; Johnson, Derek S; Chen, Youhai; O'Neill, Luke A J
- 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.
- Publication
Nature immunology, 2010, Vol 11, Issue 2, p141
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.1828