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Báo cáo y học: "A novel model of common Toll-like receptor 4- and injury-induced transcriptional themes in human leukocytes"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: A novel model of common Toll-like receptor 4- and injury-induced transcriptional themes in human leukocytes. | Haimovich et al. Critical Care 2010 14 R177 http ccforum.eom content 14 5 R177 c CRITICAL CARE RESEARCH Open Access A novel model of common Toll-like receptor 4- and injury-induced transcriptional themes in human leukocytes Beatrice Haimovich Michael T Reddell Jacqueline E Calvano Steve E Calvano Marie A Macor Susette M Coyle Stephen F Lowry Abstract Introduction An 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. Methods PBL 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. Results We 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 .