Open AccessKEY INFLAMMATORY SIGNALING PATHWAYS ARE REGULATED BY THE PROTEASOME
Author(s) -
Jing Shen,
Júlia Reis,
David C. Morrison,
Christopher J. Papasian,
Sreekumar Raghavakaimal,
Christopher P. Kolbert,
Asaf A. Qureshi,
Stefanie N. Vogel,
Nilofer Qureshi
Publication year - 2006
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/01.shk.0000209554.46704.64
Subject(s) - lactacystin , proteasome , signal transduction , sepsis , lipopolysaccharide , biology , microbiology and biotechnology , microarray analysis techniques , septic shock , proteasome inhibitor , gene , immunology , gene expression , genetics
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.