Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S
Department of Biochemistry, Hyogo College of Medicine, Japan.
J Immunol. 1999 Apr 1;162(7):3749-52.
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.
果蝇Toll蛋白的人类同源物（hToll），也称为Toll样受体4（TLR4），是白细胞介素-1/Toll受体家族中最近克隆出的一种受体。有趣的是，TLR4基因已被定位到与Lps基因座（内毒素无反应基因座）相同的区域。为了研究TLR4在LPS反应性中的作用，我们培育出了缺乏TLR4的小鼠。来自TLR4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低反应性的C3H/HeJ小鼠非常相似。此外，C3H/HeJ小鼠在TLR4的细胞质部分存在一个氨基酸单点突变，该氨基酸在白细胞介素-1/Toll受体家族中高度保守。野生型TLR4而非C3H/HeJ小鼠的突变型TLR4的过表达激活了核因子κB。综上所述，本研究表明TLR4是调节LPS反应的基因产物。
