The TLR4+896 polymorphism is not associated with lipopolysaccharide hypo-responsiveness in leukocytes

被引:27
作者
Imahara, SD [1 ]
Jelacic, S [1 ]
Junker, CE [1 ]
O'Keefe, GE [1 ]
机构
[1] Univ Washington, Harborview Med Ctr, Dept Surg, Seattle, WA 98104 USA
关键词
monocyte; polymorphism; TLR4; p38; cytokines; endotoxin;
D O I
10.1038/sj.gene.6364147
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:37 / 43
页数:7
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