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| Status |
Public on Mar 28, 2015 |
| Title |
Leukocyte gene expression variation as a function of chronic caregiving stress |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
This study explored how chronic stress influences the activity of signaling pathways that regulate inflammation in the human monocyte transcriptome. The sample consisted of 33 adults caring for a family member with glioblastoma, a terminal brain cancer, and 47 control subjects whose lives were free of major stressors. The subjects were assessed on four occasions across an eight-month period. Relative to controls, caregivers’ monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor in monocytes. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys anti-inflammatory signals to monocytes. These transcriptional disparities were not attributable to demographic or behavioral confounds. They also were not attributable to differences in diurnal cortisol output, or the abundance of glucocorticoid receptor expressed by monocytes. In ex vivo studies of monocytes stimulated with the bacterial product lipopolysaccharide, caregivers showed increased production of the pro-inflammatory cytokine interleukin-6, and were less sensitive to cortisol-mediated inhibition of this response. These findings suggest a scenario wherein chronic stressors engender functional changes that hamper monocytes’ capacity to transduce cortisol’s anti-inflammatory signals. These changes occur in parallel with, and perhaps enable, greater inflammatory signaling via nuclear-factor kappa B. The resulting inflammatory milieu could serve as a pathogenic mechanism through which chronic stressors like caregiving accentuate vulnerability to later health problems.
series type: Risk prediction
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| Overall design |
Individual differences in basal leukocyte gene expression profiles as a function of chronic caregiving stress
Characteristics included in statistical analyses of gene expression data are provided in each sample records.
Please note that educational attainment is scored as following; 0=less than high school, 1=high school diploma or equivalent, 2=associate's degree, 3=bachelor's degree, 4=masters degree, 5=doctoral degree
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| Contributor(s) |
Cole S |
| Citation(s) |
25242587 |
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| Submission date |
Nov 12, 2013 |
| Last update date |
Jan 28, 2016 |
| Contact name |
Steve Cole |
| Organization name |
UCLA School of Medicine
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| Department |
Medicine
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| Street address |
11-934 Factor Bldg, UCLA
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| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095-1678 |
| Country |
USA |
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| Platforms (1) |
| GPL10904 |
Illumina HumanHT-12 V4.0 expression beadchip (gene symbol) |
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| Samples (261)
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| Relations |
| BioProject |
PRJNA227414 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE52319_non_normalized.txt.gz |
44.6 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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