Gene expression profiles of peripheral blood leukocytes after endotoxin challenge in humans
| Autor: | Sameena S. Khan, Robert L. Danner, Debra Reda, Jennifer J. Barb, Shefali Talwar, James H. Shelhamer, Margaret Tropea, Anthony F. Suffredini, Carolea Logun, Peter J. Munson, Carmen Fiuza, Anadel Pilar Cintron |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Time Factors Physiology medicine.medical_treatment Receptors Cell Surface Inflammation Biology Endotoxin challenge Article Gene expression Genetics medicine Humans RNA Messenger Saline Oligonucleotide Array Sequence Analysis Innate immune system Healthy subjects Reproducibility of Results Middle Aged Endotoxemia Immunity Innate Peripheral blood Endotoxins Gene Expression Regulation Immunology Leukocytes Mononuclear Cytokines Female Chemokines medicine.symptom |
| Zdroj: | Physiological Genomics. 25:203-215 |
| ISSN: | 1531-2267 1094-8341 |
| DOI: | 10.1152/physiolgenomics.00192.2005 |
| Popis: | To define gene expression profiles that occur during the initial activation of human innate immunity, we administered intravenous endotoxin ( n = 8) or saline ( n = 4) to healthy subjects and hybridized RNA from blood mononuclear cells (0, 0.5, 6, 24, 168 h) or whole blood (0, 3, 6, 24, 168 h) to oligonucleotide probe arrays. The greatest change in mononuclear cell gene expression occurred at 6 h (439 induced and 428 repressed genes, 1% false discovery rate, and 50% fold change) including increased expression of genes associated with pathogen recognition molecules and signaling cascades linked to receptors associated with cell mobility and activation. Induced defense response genes included cytokines, chemokines, and their respective receptors, acute-phase transcription factors, proteases, arachidonate metabolites, and oxidases. Repressed defense response genes included those associated with co-stimulatory molecules, T and cytotoxic lymphocytes, natural killer (NK) cells, and protein synthesis. Gene expression profiles of whole blood had similar biological themes. Over 100 genes not typically associated with acute inflammation were differentially regulated after endotoxin. By 24 h, gene expression had returned to baseline values. Thus the inflammatory response of circulating leukocytes to endotoxin in humans is characterized by a rapid amplification and subsidence of gene expression. These results indicate that a single intravascular exposure to endotoxin produces a large but temporally short perturbation of the blood transcriptome. |
| Databáze: | OpenAIRE |
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