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Early Intervention by Targeting Inhibitors of Multiple Signal Transduction Pathways in LPS Induced Human PBMCs
Author(s) -
Turner Anne Elise,
Whiteman Sarah,
Jett Marti,
Mendis Chanaka
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a660-b
Subject(s) - signal transduction , peripheral blood mononuclear cell , lipopolysaccharide , septic shock , gene , microbiology and biotechnology , biology , immunology , secretion , gene expression , transduction (biophysics) , cytokine , computational biology , sepsis , genetics , in vitro , biochemistry
Lipopolysaccharide (LPS) is an endotoxin that induces the secretion of pro‐inflammatory cytokines in many cells and has been known to induce septic shock in humans. This project is aimed at developing a rapid diagnostic method to combat the effects of LPS and eventually other toxins by utilizing signal transduction pathways induced by of LPS in Peripheral Blood Mononuclear Cells (PBMC) as a prototype module. We have identified a set of LPS specific genes in human PBMCs through micro array analysis and have found signaling pathways common among these genes. A thorough investigation of the newly identified common pathways allowed us to find key pathway components that may alter the expression pattern of a set of genes and have the potential to act as diagnostic markers before symptoms and septic shock can take effect. We will further evaluate the alterations induced by specific inhibitors of the known gene expression profile of LPS using RT‐PCR and then use ELISA to examine the effects of the inhibitors on protein expression patterns. We believe that our work will allow us to better understand the complex interactions of multiple signal transduction pathways induced by LPS.