Medline ® Abstract for Reference 76
of 'Toll-like receptors: Roles in disease and therapy'
76
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The TLR4 +896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes.
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Imahara SD, Jelacic S, Junker CE, O'Keefe GE
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Genes Immun. 2005;6(1):37.
Toll-like receptor 4 (TLR-4) is required for detection of Gram negative bacterial infections by binding lipopolysaccharide (LPS) and for the initiation of inflammatory signaling. Recent studies have demonstrated that a nonsynonymous single-nucleotide polymorphism (Asp299Gly, A+896G) is associated with decreased endotoxin responsiveness and poor outcomes from sepsis. We show that human carriers of this polymorphism show no deficit in LPS induced peripheral blood mononuclear cell (PBMC) mitogen-activated protein kinase (MAPK) activity, no reduction in sensitivity to endotoxin, and variable differences in whole-blood inflammatory cytokine production. These results indicate that this mutation is not a primary determinant of human endotoxin sensitivity.
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Department of Surgery, University of Washington and Harborview Medical Center, Seattle, Washington 98104, USA. imaharas@u.washington.edu
PMID