| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communications |
From the Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan
During sepsis the host’s system-wide response to microbial invasion seems dysregulated. Here we explore the diverse multiorgan transcriptional programs activated during systemic inflammation in a cecal ligation/puncture model of sepsis in rats. Using DNA microarrays representing 7398 genes, we examined the temporal sequence of sepsis-induced gene expression patterns in major organ systems including lung, liver, kidney, thymus, spleen, and brain. Although genes known to be associated with systemic inflammation were identified by our global transcript analysis, many genes and expressed sequence tags not previously linked to the septic response were also elucidated. Taken together, our results suggest activation of a highly complex transcriptional response in individual organs of the septic animal. Several overlying themes emerged from our genome-scale analysis that includes 1) the sepsis response elicited gene expression profiles that were either organ-specific, common to more than one organ, or distinctly opposite in some organs; 2) the brain is protected from sepsis-induced gene activation relative to other organs; 3) the thymus and spleen have an interesting cohort of genes with opposing gene expression patterns; 4) genes with proinflammatory effects were often balanced by genes with anti-inflammatory effects (eg, interleukin-1ß/decoy receptor, xanthine oxidase/superoxide dismutase, Ca2+-dependent PLA2/Ca2+-independent PLA2); and 5) differential gene expression was observed in proteins responsible for preventing tissue injury and promoting homeostasis including anti-proteases (TIMP-1, Cpi-26), oxidant neutralizing enzymes (metallothionein), cytokine decoy receptors (interleukin-1RII), and tissue/vascular permeability factors (aquaporin 5, vascular endothelial growth factor). This global perspective of the sepsis response should provide a molecular framework for future research into the pathophysiology of systemic inflammation. Understanding, on a genome scale, how an organism responds to infection, may facilitate the development of enhanced detection and treatment modalities for sepsis.
This article has been cited by other articles:
 |
|
 |
|
  R. A. Lukaszewski, A. M. Yates, M. C. Jackson, K. Swingler, J. M. Scherer, A. J. Simpson, P. Sadler, P. McQuillan, R. W. Titball, T. J. G. Brooks, et al. Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients Clin. Vaccine Immunol., July 1, 2008; 15(7): 1089 - 1094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. R. Wong, T. P. Shanley, B. Sakthivel, N. Cvijanovich, R. Lin, G. L. Allen, N. J. Thomas, A. Doctor, M. Kalyanaraman, N. M. Tofil, et al. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome Physiol Genomics, July 18, 2007; 30(2): 146 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. SCHNEIDER, M. WEISS, W. DU, G. LEDER, K. BUTTENSCHON, U. C LIENER, and U. B BRUCKNER MAPKinase Gene Expression, as Determined by Microarray Analysis, Distinguishes Uncomplicated from Complicated Reconstitution after Major Surgical Trauma Ann. N.Y. Acad. Sci., December 1, 2006; 1090(1): 429 - 444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-M. Cavaillon and D. Annane Invited review: Compartmentalization of the inflammatory response in sepsis and SIRS Innate Immunity, June 1, 2006; 12(3): 151 - 170. [Abstract] [PDF]
|
|
|
|
 |
|
 N. G. Hall, Y. Liu, J. M. Hickman-Davis, G. C. Davis, C. Myles, E. J. Andrews, S. Matalon, and J. D. Lang Jr. Bactericidal Function of Alveolar Macrophages in Mechanically Ventilated Rabbits Am. J. Respir. Cell Mol. Biol., June 1, 2006; 34(6): 719 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. T. Morgan, Z. Jayyosi, M. A. Hower, M. V. Pino, T. M. Connolly, K. Kotlenga, J. Lin, M. Wang, H.-L. Schmidts, M. S. Bonnefoi, et al. The Hepatic Transcriptome as a Window on Whole-Body Physiology and Pathophysiology Toxicol Pathol, January 1, 2005; 33(1): 136 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Shi, K. Takahashi, J. Dundee, S. Shahroor-Karni, S. Thiel, J. C. Jensenius, F. Gad, M. R. Hamblin, K. N. Sastry, and R. A. B. Ezekowitz Mannose-binding Lectin-deficient Mice Are Susceptible to Infection with Staphylococcus aureus J. Exp. Med., May 17, 2004; 199(10): 1379 - 1390. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Liu, S. M. Dhanasekaran, H. Jin, B. Hu, S. A. Tomlins, A. M. Chinnaiyan, and S. H. Phan FIZZ1 Stimulation of Myofibroblast Differentiation Am. J. Pathol., April 1, 2004; 164(4): 1315 - 1326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Matthay, G. A. Zimmerman, C. Esmon, J. Bhattacharya, B. Coller, C. M. Doerschuk, J. Floros, M. A. Gimbrone Jr, E. Hoffman, R. D. Hubmayr, et al. Future Research Directions in Acute Lung Injury: Summary of a National Heart, Lung, and Blood Institute Working Group Am. J. Respir. Crit. Care Med., April 1, 2003; 167(7): 1027 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Liu, Y. Yu, Y. Jiang, and J. Li Growth Hormone Increases Lung NF-{kappa}B Activation and Lung Microvascular Injury Induced by Lipopolysaccharide in Rats Ann. Clin. Lab. Sci., April 1, 2002; 32(2): 164 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Kumar-Sinha, S. Varambally, A. Sreekumar, and A. M. Chinnaiyan Molecular Cross-talk between the TRAIL and Interferon Signaling Pathways J. Biol. Chem., January 4, 2002; 277(1): 575 - 585. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
