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Differential Gene Expression in Gram-negative and Gram-positive Sepsis

Department of Surgery, Department of Medical Research, and Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine; Institute of Biomedical Sciences, Academia Sinica, Taipei; and Institute of Biomedical Sciences, and Molecular Biology, National Chung Hsing University, Taichung, Taiwan

Correspondence and requests for reprints should be addressed to Fang-Yue Lin, M.D., Ph.D., Department of Surgery, National Taiwan University Hospital, No. 7, Chung Shan South Road, Taipei, 100, Taiwan, Republic of China. E-mail: fylin1{at}ha.mc.ntu.edu.tw

Sepsis is the most common cause of death in patients in the intensive care unit. Genome-wide gene expression analysis can provide insights into the molecular alterations of sepsis. Total mRNA was extracted from the livers of 6 uninfected control mice and 60 septic mice after infusion of either live Escherichia coli or Staphylococcus aureus. Using a murine complementary DNA microarray system, changes in gene expression were monitored at six time points (uninfected, 2, 8, 24, 48, and 72 hours). Overall, 4.8% of 6,144 assessed genes were differentially regulated with a greater than twofold change across all time points. Most of the genes with altered expression were commonly present in gram-negative and gram-positive sepsis, but the expression levels of 17 genes were different between both types of sepsis at particular time points after infection. The microarray results support the hypothesis that both gram-positive and gram-negative sepsis share a final common pathway involved in the pathogenesis of sepsis, but certain genes are differentially expressed under distinct regulation. These results may provide insights into the pathogenesis of sepsis and may also help identify some altered genes that can serve as new targets for diagnostic tools and therapeutic strategies.

Key Words: bacterial infection • liver • microarray

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