Social regulation of gene expression in human leukocytes

Autor: Caroline Y. Sung, Steve W. Cole, John T. Cacioppo, Louise C. Hawkley, Robert M. Rose, Jesusa M.G. Arevalo
Rok vydání: 2007
Předmět:
Male
0302 clinical medicine
Models
Gene expression
Leukocytes
2.1 Biological and endogenous factors
Aetiology
Promoter Regions
Genetic
Genetics
Regulation of gene expression
0303 health sciences
Genome
biology
Middle Aged
Biological Sciences
C-Reactive Protein
Female
Social genomics
Glucocorticoid
Signal Transduction
Human
Biotechnology
medicine.drug
Bioinformatics
1.1 Normal biological development and functioning
CREB
Models
Biological
Promoter Regions
03 medical and health sciences
Genetic
Clinical Research
Underpinning research
Information and Computing Sciences
medicine
Humans
Interpersonal Relations
Glucocorticoids
Gene
Transcription factor
Aged
030304 developmental biology
Genome
Human
Research
Inflammatory and immune system
Human Genome
Computational Biology
Biological
Good Health and Well Being
IRF1
Gene Expression Regulation
biology.protein
Generic health relevance
Environmental Sciences
030217 neurology & neurosurgery
Zdroj: Genome biology, vol 8, iss 9
Genome Biology
ISSN: 1474-760X
DOI: 10.1186/gb-2007-8-9-r189
Popis: Analysis of differentially expressed in circulating leukocytes from people who chronically experienced high versus low levels of subjective social isolation (loneliness) revealed over-expression of some anti-inflammatory genes and under-expression of some pro-inflammatory genes.
Background Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. Results DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-κB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti-inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/EBP, Oct, and GATA pathways. Conclusion These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation.
Databáze: OpenAIRE
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