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Series GSE46268 Query DataSets for GSE46268
Status Public on Dec 31, 2013
Title Gene expression profile of human monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25a-dihydroxyvitamin D3 (1,25D3)
Organism Homo sapiens
Experiment type Expression profiling by array
Summary A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the antimicrobial mechanism is unclear. Here, we demonstrate that vitamin A mediates host defense through regulation of cellular cholesterol content. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3, the biologically active forms of vitamin A and vitamin D respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Gene expression profiling reveals that ATRA but not 1,25D3 triggers a lipid metabolism and efflux pathway, including expression of lysosomal lipid transport gene NPC2. ATRA-induced decrease in total cellular cholesterol content, subcellular lipid reorganization, lysosomal acidification and antimicrobial activity are all dependent upon expression of NPC2. Finally, the addition of HIV-protease inhibitors known to inhibit cholesterol efflux, Ritonavir and Nelfinavir, blocked both ATRA-induced cholesterol decrease as well as antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated host defense mechanism against M. tuberculosis requires regulation of cellular cholesterol.
 
Overall design Monocytes derived from four independent healthy blood donors that were stimulated with control (CTRL), ATRA or 1,25D3 at 10-8M for 18 hours.
 
Contributor(s) Wheelwright M, Kim EW, DeLeon A, Krutzik SR, Liu PT
Citation(s) 24501203
Submission date Apr 22, 2013
Last update date Mar 25, 2019
Contact name Philip T. Liu
E-mail(s) ptliu@mednet.ucla.edu
Phone 310-206-8457
Organization name University of California at Los Angeles
Department Department of Orthopaedic Surgery
Lab Liu Lab
Street address 615 Charles E Young Drive South, 410 OHRC
City Los Angeles
State/province CA
ZIP/Postal code 90095
Country USA
 
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (12)
GSM1127890 monocyte from donor 1 stimulated with CTRL
GSM1127891 monocyte from donor 2 stimulated with CTRL
GSM1127892 monocyte from donor 3 stimulated with CTRL
Relations
BioProject PRJNA198494

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE46268_RAW.tar 65.9 Mb (http)(custom) TAR (of CEL, CHP)
Raw data provided as supplementary file
Processed data included within Sample table
Processed data provided as supplementary file

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