Toll-like receptor 4 expression levels determine the degree of LPS-susceptibility in mice
Toll-like receptor 4 expression levels determine the degree of LPS-susceptibility in mice
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DOI：
10.1002/eji.200323431
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发表时间：
2003-03-01
影响因子：
5.4
通讯作者：
Freudenberg, MA
中科院分区：
文献类型：
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作者：
Kalis, C;Kanzler, B;Freudenberg, MA
C57BL/10ScCr （Cr）小鼠携带toll样受体4（tlr4）基因缺失（即它们是tlr4(0/0)），因此对LPS的作用难以耐受。将野生型tlr4转基因基因插入到tlr4(0/0) Cr种系中，使所创建的两个转基因系对LPS具有敏感性，表明tlr4是Cr小鼠对LPS反应的唯一限制因子。杂合子转基因（tlr4(Tr/0)）、野生型C57BL/10ScSn (Sn) （tlr4(+/+)）和杂合子F1 (Sn × Cr) （tlr4(+/0)）小鼠的tlr4 mRNA表达绝对水平差异显著。然而，在所有菌株中，不同器官的表达分布模式是相同的。在不同的生物学试验（B细胞有丝分裂性、细胞因子诱导和致死毒性）中，不同品系小鼠对LPS的反应程度与t1r4 mRNA的表达水平相关。在巨噬细胞中，对lps诱导的细胞因子（IL-6）应答的研究显示，应答与TLR4-MD-2水平的对数呈线性关系。
C57BL/10ScCr (Cr) mice carry a deletion of the Toll-like receptor 4 (tlr4) gene (i.e. they are tlr4(0/0)) and are thus refractory to LPS effects. Insertion of wild-type tlr4 transgene into the tlr4(0/0) Cr germ line endowed LPS susceptibility in the two transgenic lines created, indicating that TLR4 is the only limiting factor for LPS responsiveness in Cr mice. The absolute levels of tlr4 mRNA expressed by the heterozygous transgenic (tlr4(Tr/0)), wild-type C57BL/10ScSn (Sn) (tlr4(+/+)) and heterozygous F1 (Sn x Cr) (tlr4(+/0)) mice varied markedly. However, the pattern of distribution of expression in the different organs was the same in all strains. In different biological assays (B cell mitogenicity, cytokine induction and lethal toxicity) the degree of LPS response obtained in the different strains of mice correlated with the levels of t1r4 mRNA expression. In macrophages, investigation of the LPS-induced cytokine (IL-6) response revealed a linear relationship between the response and the logarithm of TLR4-MD-2 levels.