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| 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
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| 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.
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| 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.
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| Contributor(s) |
Wheelwright M, Kim EW, DeLeon A, Krutzik SR, Liu PT |
| Citation(s) |
24501203 |
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| Submission date |
Apr 22, 2013 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Philip T. Liu |
| E-mail(s) |
ptliu@mednet.ucla.edu
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| Phone |
310-206-8457
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| Organization name |
University of California at Los Angeles
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| Department |
Department of Orthopaedic Surgery
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| Lab |
Liu Lab
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| Street address |
615 Charles E Young Drive South, 410 OHRC
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (12)
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| GSM1127890 |
monocyte from donor 1 stimulated with CTRL |
| GSM1127891 |
monocyte from donor 2 stimulated with CTRL |
| GSM1127892 |
monocyte from donor 3 stimulated with CTRL |
| GSM1127893 |
monocyte from donor 4 stimulated with CTRL |
| GSM1127894 |
monocyte from donor 1 stimulated with ATRA |
| GSM1127895 |
monocyte from donor 2 stimulated with ATRA |
| GSM1127896 |
monocyte from donor 3 stimulated with ATRA |
| GSM1127897 |
monocyte from donor 4 stimulated with ATRA |
| GSM1127898 |
monocyte from donor 1 stimulated with 1,25D |
| GSM1127899 |
monocyte from donor 2 stimulated with 1,25D |
| GSM1127900 |
monocyte from donor 3 stimulated with 1,25D |
| GSM1127901 |
monocyte from donor 4 stimulated with 1,25D |
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| Relations |
| BioProject |
PRJNA198494 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46268_RAW.tar |
65.9 Mb |
(http)(custom) |
TAR (of CEL, CHP) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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