Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptomics of vitamin D treatment effects in Mycobacterium tuberculosis-infected THP-1 cells


ABSTRACT: Previous reports have shown low vitamin D serum levels and polymorphisms in the vitamin D receptor (VDR) to be associated with increased risk for TB. Given that 1?,25-dihydroxyvitamin D3 has a role in lipid metabolism control, we tested whether the link between 1?,25-dihydroxyvitamin D3 and tuberculosis involves macrophage lipid metabolism. Since formation of lipid droplets (LD) is a hallmark of lipid dysregulation in M. tuberculosis-infected macrophages, we measured LD content as a readout of altered lipid metabolism in infected THP-1 cells. Induction of LD, which peaked by 24 hours post-infection was prevented by addition of 1?,25-dihydroxyvitamin D3 at the time of infection. To investigate the mechanism of 1?,25-dihydroxyvitamin D3 modulation of LD formation, we analyzed the transcriptome of M. tuberculosis-infected THP-1 cells with and without 1?,25-dihydroxyvitamin D3 treatment. THP-1 cells were cultured in 24-well flat bottom plates, pre-treated with 20ng/ml PMA for 24 h, and incubated with M. tuberculosis H37Rv. After 4 hours of infection, cells were washed to remove extracellular bacteria and treated with 100 nM of 1?,25-dihydroxyvitamin D3. THP-1 cells were collected and analyzed at 24h. 3 biological replicates in each of the 4 groups were prepared: Infected, Infected plus 1?,25-dihydroxyvitamin D3, Non-infected, Non-infected plus 1?,25-dihydroxyvitamin D3.

ORGANISM(S): Homo sapiens

SUBMITTER: Hugh Salamon 

PROVIDER: E-GEOD-57028 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Cutting edge: Vitamin D regulates lipid metabolism in Mycobacterium tuberculosis infection.

Salamon Hugh H   Bruiners Natalie N   Lakehal Karim K   Shi Lanbo L   Ravi Janani J   Yamaguchi Ken D KD   Pine Richard R   Gennaro Maria Laura ML  

Journal of immunology (Baltimore, Md. : 1950) 20140604 1


Vitamin D has long been linked to resistance to tuberculosis, an infectious respiratory disease that is increasingly hard to treat because of multidrug resistance. Previous work established that vitamin D induces macrophage antimicrobial functions against Mycobacterium tuberculosis. In this article, we report a novel, metabolic role for vitamin D in tuberculosis identified through integrated transcriptome and mechanistic studies. Transcriptome analysis revealed an association between vitamin D r  ...[more]

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