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| Status |
Public on Jan 05, 2013 |
| Title |
1,25-Dihydroxyvitamin D Promotes Negative Feedback Regulation of Toll-Like Receptor Signaling via Targeting MicroRNA-155-SOCS1 in Macrophages |
| Platform organisms |
Homo sapiens; Mus musculus; Rattus norvegicus; Human alphaherpesvirus 1; Human betaherpesvirus 5; Murid betaherpesvirus 1; human gammaherpesvirus 4; JC polyomavirus; Human immunodeficiency virus 1; Murid gammaherpesvirus 4; Human gammaherpesvirus 8; Betapolyomavirus hominis; Betapolyomavirus macacae |
| Sample organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
The negative feedback mechanism is essential to maintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25(OH)2D3) modulates innate immune response, but the mechanism remains poorly understood. Here we report that vitamin D receptor (VDR) signaling attenuates Toll-like receptor-mediated inflammation by enhancing the negative feedback inhibition. VDR inactivation leads to a hyperinflammatory response in mice and macrophage cultures when challenged with lipopolysaccharide (LPS) due to miR-155 overproduction that excessively suppresses SOCS1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)2D3 stimulates SOCS1 by down-regulating miR-155. 1,25(OH)2D3 down-regulates bic transcription by inhibiting NF-kappaB activation, which is mediated by a kappaB cis-DNA element located within the first intron of the bic gene. Together these data identify a novel regulatory mechanism for vitamin D to control innate immunity.
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| Overall design |
MicroRNA arrays. Total RNAs were extracted from RAW264.7 cells (mouse macrophage line) treated with LPS (100ng/ml) in the presence or absence of 1,25(OH)2D3 (20 nM) overnight. MicroRNA profiling was performed using the miRCURY LNA microRNA Arrays (Exiqon, Vedvaek,Denmark) according to the manufacture'¹s standard protocols. The arrays were scanned with the GenePix 4000B scanner using the manufacturer's recommended settings. The raw data was extracted using GenePix Pro and imported into GeneSpring GX10 for analyses.
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| Contributor(s) |
Chen Y, Liu W, Sun T, Huang Y, Wang Y, Deb DK, Yoon D, Kong J, Thadhani R, Li YC |
| Citation(s) |
23436936 |
| Submission date |
Jan 04, 2013 |
| Last update date |
May 10, 2016 |
| Contact name |
Yong Huang |
| E-mail(s) |
yh9fj@virginia.edu
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| Phone |
(434) 243-0842
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| Organization name |
University of Viginia
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| Department |
Medicine
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| Street address |
1340 Jefferson Park Ave
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| City |
Charlottesville |
| State/province |
VA |
| ZIP/Postal code |
22908 |
| Country |
USA |
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| Platforms (1) |
| GPL7723 |
miRCURY LNA microRNA Array, v.11.0 - hsa, mmu & rno |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA185321 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43300_RAW.tar |
2.3 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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