Key inflammatory signaling pathways are regulated by the proteasome

Lipopolysaccharide (LPS) is a major structural component of all Gram-negative organisms and has been implicated in Gram-negative sepsis and septic shock. In the present study, Affymetrix microarray analysis of RNA derived from murine macrophages treated with LPS in the absence or presence of the pro...

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Published in:Shock (Augusta, Ga.) Ga.), 2006-05, Vol.25 (5), p.472-484
Main Authors: JING SHEN, REIS, Julia, MORRISON, David C, PAPASIAN, Christopher, RAGHAVAKAIMAL, Sreekumar, KOLBERT, Christopher, QURESHI, Asaf A, VOGEL, Stefanie N, QURESHI, Nilofer
Format: Article
Language:English
Subjects:
Acetylcysteine - analogs & derivatives
Acetylcysteine - metabolism
Acetylcysteine - pharmacology
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Blood coagulation. Blood cells
Cell Survival
Chymotrypsin - pharmacology
Emergency and intensive care: infection, septic shock
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic
General aspects, investigation methods, hemostasis, fibrinolysis
Inflammation
Intensive care medicine
Lipopolysaccharides - metabolism
Macrophages - metabolism
Medical sciences
Mice
Molecular and cellular biology
Oligonucleotide Array Sequence Analysis
Proteasome Endopeptidase Complex - metabolism
Proteasome Endopeptidase Complex - physiology
Shock, Septic - metabolism
Signal Transduction
Toll-Like Receptor 4 - metabolism
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Summary:Lipopolysaccharide (LPS) is a major structural component of all Gram-negative organisms and has been implicated in Gram-negative sepsis and septic shock. In the present study, Affymetrix microarray analysis of RNA derived from murine macrophages treated with LPS in the absence or presence of the proteasome inhibitor lactacystin revealed that the vast majority of genes regulated by LPS is under control of the proteasome. Analysis of the data has revealed that the products of these genes participate in 14 distinct signaling pathways. This represents a novel approach to the identification of signaling pathways that are both toll-like receptor 4- and proteasome-dependent and may lead to the development of new drug targets in Gram-negative sepsis and septic shock.
ISSN:1073-2322
1540-0514
DOI:10.1097/01.shk.0000209554.46704.64