Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
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DOI：
10.4049/jimmunol.162.7.3749
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发表时间：
1999-04
影响因子：
4.4
通讯作者：
K. Hoshino;O. Takeuchi;T. Kawai;H. Sanjo;T. Ogawa;Y. Takeda;K. Takeda;S. Akira
中科院分区：
文献类型：
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作者：
K. Hoshino;O. Takeuchi;T. Kawai;H. Sanjo;T. Ogawa;Y. Takeda;K. Takeda;S. Akira
果蝇Toll的人类同源物（hToll），也称为Toll样受体4（TLR 4），是最近克隆的IL-1/Toll受体家族的受体。有趣的是，TLR 4基因已定位于与LPS基因座（内毒素无反应基因座）定位的相同区域。为了检测TLR 4在LPS应答中的作用，我们产生了缺乏TLR 4的小鼠。TLR 4缺陷小鼠的巨噬细胞和B细胞对LPS无反应。所有这些表现与LPS低应答C3 H/HeJ小鼠的表现非常相似。此外，C3 H/HeJ小鼠在TLR 4的胞质部分中具有在IL-1/Toll受体家族中高度保守的氨基酸的单点突变。C3 H/HeJ小鼠野生型TLR 4的过表达而非突变型TLR 4激活NF-κ B。总之，本研究表明TLR 4是调节LPS反应的基因产物。
The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-kappaB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.