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| Status |
Public on Sep 25, 2019 |
| Title |
Cigarette smoke preparations, but not moist snuff, impair expression of genes involved in signaling and cytolytic functions in peripheral blood mononuclear cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Cigarette smoking exerts diverse physiological effects including immune suppression. Existing US epidemiological data show that consumption of smokeless tobacco products, such as moist snuff, is less harmful relative to cigarette smoking. In efforts to understand the molecular changes due to consumption of different tobacco product classes, we have shown recently that smokers exhibit distinct peripheral blood mononuclear cells (PBMCs) gene expression patterns relative to moist snuff users and non-tobacco consumers (NTCs). To better characterize the biological effects exerted from the use of different tobacco products, a genome-wide gene expression study, using a cultured PBMC model, was performed.
Gene expression profiles from PBMCs treated with low equi-nicotine units (0.3 µg/ml) of WS-CM and a single high dose of STE (100 µg/ml) were similar to those from untreated controls. Cells treated with medium and high equi-nicotine unit doses of WS-CM (1.0 and 3.0 µg/ml) exhibited significantly different gene expression profiles compared to the low equi-nicotine WS-CM dose and STE. Pre-treatment with higher doses of WS-CM inhibited the expression of several pro-inflammatory genes that regulate immune responses, including IFNγ, TNFα, and IL-2. Gene expression changes of these genes and other cytokine signaling genes were confirmed by qRT-PCR. Moreover, secretion of IFNγ, TNFα and IL-2 proteins was abolished by WS-CM pre-treatment even after 24 hours of toll like receptor stimulation. Additionally, pathway analyses revealed that higher doses of WS-CM inhibited NF-ĸβ signaling and a wide range of signaling pathways associated with immune cell differentiation and inflammatory responses, and increased expression of genes involved in apoptosis. Collectively, our results show that pre-treatment of PBMCs with higher doses of WS-CM inhibits immune activation and effector cytokine expression and secretion, resulting in a reduced immune response, whereas STE had minimal effect.
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| Overall design |
To understand how different tobacco products impact immune responses, we assessed transcriptomic profiles in peripheral blood mononuclear cells (PBMCs) pretreated with Whole Smoke Conditioned-Medium (WS-CM) or Smokeless Tobacco Extracts (STE), and stimulated with lipopolysaccharide, phorbol myristate and ionomycin (agonists).
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| Contributor(s) |
Liu G, Prasad GL |
| Citation(s) |
31527707 |
| Submission date |
Mar 07, 2019 |
| Last update date |
Jan 14, 2020 |
| Contact name |
Prasad GL |
| E-mail(s) |
biomarker@rjrt.com
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| Phone |
336-741-7562
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| Organization name |
RAISC
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| Street address |
401 N Main St
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| City |
Winston-salem |
| State/province |
NC |
| ZIP/Postal code |
27101 |
| Country |
USA |
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| Platforms (1) |
| GPL17586 |
[HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version] |
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| Samples (19)
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| Relations |
| BioProject |
PRJNA525969 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE127977_RAW.tar |
465.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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