NDLI: miR-451 regulates dendritic cell cytokine responses to influenza infection.

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miR-451 regulates dendritic cell cytokine responses to influenza infection.

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miR-451 regulates dendritic cell cytokine responses to influenza infection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Weiss, Mitchell J. Podyminogin, Rebecca L. Zhao, Guo-Wei Navarro, Garnet Rosenberger, Carrie M. Aderem, Alan Askovich, Peter S.
Description	Country affiliation: United States Author Affiliation: Rosenberger CM ( Seattle Biomedical Research Institute, Seattle, WA 98109, USA. rosenberger.carrie@gene.com)
Abstract	MicroRNAs (miRNAs) are important posttranscriptional regulators in immune cells, but how viral infection regulates miRNA expression to shape dendritic cell (DC) responses has not been well characterized. We identified 20 miRNAs that were differentially expressed in primary murine DCs in response to the dsRNA agonist polyinosinic-polycytidylic acid, a subset of which were modestly regulated by influenza infection. miR-451 was unique because it was induced more strongly in primary splenic and lung DCs by live viral infection than by purified agonists of pattern recognition receptors. We determined that miR-451 regulates a subset of proinflammatory cytokine responses. Three types of primary DCs treated with antisense RNA antagomirs directed against miR-451 secreted elevated levels of IL-6, TNF, CCL5/RANTES, and CCL3/MIP1 , and these results were confirmed using miR-451(null) cells. miR-451 negatively regulates YWHAZ/14-3-3Î¶ protein levels in various cell types, and we measured a similar inhibition of YWHAZ levels in DCs. It is known that YWHAZ can control the activity of two negative regulators of cytokine production: FOXO3, which is an inhibitory transcription factor, and ZFP36/Tristetraprolin, which binds to AU-rich elements within 3'-untranslated regions to destabilize cytokine mRNAs. Inhibition of miR-451 expression correlated with increased YWHAZ protein expression and decreased ZFP36 expression, providing a possible mechanism for the elevated secretion of IL-6, TNF, CCL5/RANTES, and CCL3/MIP1 . miR-451 levels are themselves increased by IL-6 and type I IFN, potentially forming a regulatory loop. These data suggest that viral infection specifically induces a miRNA that directs a negative regulatory cascade to tune DC cytokine production.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1201437
Journal	The Journal of Immunology
Issue Number	12
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-12-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cytokines Biosynthesis Dendritic Cells Immunology Virology Micrornas Physiology Animals Cell Line, Tumor Antagonists & Inhibitors Metabolism Down-regulation Gene Expression Regulation, Viral Influenza A Virus, H1n1 Subtype Influenza A Virus, H3n2 Subtype Melanoma, Experimental Mice Mice, 129 Strain Mice, Inbred C57bl Mice, Knockout Genetics Orthomyxoviridae Infections Primary Cell Culture Up-regulation Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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