ArticleCritical care (London, England)2010
A novel model of common Toll-like receptor 4- and injury-induced transcriptional themes in human leukocytes.
Article in Critical care (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Tissue-Specific Differential Expression of Novel Genes and Long Intergenic Noncoding RNAs in Humans With Extreme Response to Evoked Endotoxemia.Circulation. Genomic and precision medicine · 2018Trial
- Long noncoding RNA GSEC promotes neutrophil inflammatory activation by supporting PFKFB3-involved glycolytic metabolism in sepsis.Cell death & disease · 2021Article
- Review
- Immunometabolism and Sepsis: A Role for HIF?Frontiers in molecular biosciences · 2019Review
- Human metabolic response to systemic inflammation: assessment of the concordance between experimental endotoxemia and clinical cases of sepsis/SIRS.Critical care (London, England) · 2015Article
- Physiologic variability at the verge of systemic inflammation: multiscale entropy of heart rate variability is affected by very low doses of endotoxin.Shock (Augusta, Ga.) · 2015Article
- Cellular metabolic regulators: novel indicators of low-grade inflammation in humans.Annals of surgery · 2014Article
- Predicting critical transitions in a model of systemic inflammation.Journal of theoretical biology · 2013Article
- Toll like receptor signaling in "inflammaging": microRNA as new players.Immunity & ageing : I & A · 2013Article
- Gene expression profiles in alveolar macrophages induced by lipopolysaccharide in humans.Molecular medicine (Cambridge, Mass.) · 2012Article
- Disruption of rhythms of molecular clocks in primary synovial fibroblasts of patients with osteoarthritis and rheumatoid arthritis, role of IL-1β/TNF.Arthritis research & therapy · 2012Article
- Modeling autonomic regulation of cardiac function and heart rate variability in human endotoxemia.Physiological genomics · 2011Article
- Roles of SIRT1 in the acute and restorative phases following induction of inflammation.The Journal of biological chemistry · 2010Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
introductionAn endotoxin challenge, sepsis, and injury/trauma, trigger significant changes in human peripheral blood leukocytes (PBL) gene expression. In this study, we have sought to test the hypothesis that the Toll-like receptor 4 (TLR4) induced transcription patterns elicited in humans exposed to in vivo endotoxin would parallel gene expression patterns observed in trauma patients with initial non-infectious injury. In addition, we sought to identify functional modules that are commonly affected by these two insults of differing magnitude and duration.
methodsPBL were obtained from seven adult human subject experimental groups. The groups included a group of healthy, hospitalized volunteers (n = 15), that comprised four study groups of subjects challenged with intravenous endotoxin, without or with cortisol, and two serial samplings of trauma patients (n = 5). The PBL were analyzed for gene expression using a 8,793 probe microarray platform (Gene Chip® Focus, Affymetrix). The expression of a subset of genes was determined using qPCR.
resultsWe describe sequential selection criteria of gene expression data that identifies 445 genes that are significantly differentially expressed (both P ≤ 0.05 and > 1.2 fold-change) in PBL derived from human subjects during the peak of systemic inflammatory responses induced by in vivo endotoxin, as well as in PBL obtained from trauma patients at 1 to 12 days after admission. We identified two functional modules that are commonly represented by this analysis. The first module includes more than 50 suppressed genes that encode ribosomal proteins or translation regulators. The second module includes up-regulated genes encoding key enzymes associated with glycolysis. Finally, we show that several circadian clock genes are also suppressed in PBL of surgical ICU patients.
conclusionsWe identified a group of > 400 genes that exhibit similar expression trends in PBL derived from either endotoxin-challenged subjects or trauma patients. The suppressed translational and circadian clock modules, and the upregulated glycolytic module, constitute a robust and long lasting PBL gene expression signature that may provide a tool for monitoring systemic inflammation and injury.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.