Cutting edge: Naturally occurring soluble form of mouse toll-like receptor 4 inhibits lipopolysaccharide signaling
Cutting edge: Naturally occurring soluble form of mouse toll-like receptor 4 inhibits lipopolysaccharide signaling
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DOI：
10.4049/jimmunol.165.12.6682
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发表时间：
2000-12-15
影响因子：
4.4
通讯作者：
Yoshikai, Y
中科院分区：
文献类型：
--
作者：
Iwami, K;Matsuguchi, T;Yoshikai, Y
Toll样受体（TLR）是一类在宿主防御中起重要作用的蛋白质家族。功能性TLR 4缺陷的小鼠对LPS反应迟钝，表明TLR 4对于LPS信号传导是必需的。本研究克隆了一种可变剪接的小鼠TLR 4（mTLR 4）mRNA，该mRNA位于已报道的mTLR 4基因的第二和第三外显子之间，含有一个符合读框的终止密码子，编码已报道的mTLR 4基因的86个氨基酸和另外的36个氨基酸，该可变剪接的mTLR 4 mRNA表达一种部分分泌的20-kDa蛋白，在小鼠巨噬细胞系中，外源表达的smTLR 4显著抑制LPS介导的TNF-α产生和NF-κ B活化。此外，在小鼠巨噬细胞中，LPS增加了smTLR 4的mRNA。综上所述，我们的结果表明，smTLR 4可能作为一种反馈机制来抑制小鼠巨噬细胞中过度的LPS反应。
Toll-like receptors (TLRs) are a family of proteins playing important roles in host defense. Mice defective of functional TLR4 are hyporesponsive to LPS, suggesting that TLR4 is essential for LPS signaling. Here we report the cloning of an alternatively spliced mouse TLR4 (mTLR4) mRNA, The additional exon exists between the second and third exon of the reported mTLR4 gene and contains an in-frame stop codon, The alternatively spliced mRNA encodes 86 aa of the reported mTLR4 and an additional 36 aa, This alternatively spliced mTLR4 mRNA expressed a partially secretary 20-kDa protein, which we named soluble mTLR4 (smTLR4), In a mouse macrophage cell line, the exogenously expressed smTLR4 significantly inhibited LPS-mediated TNF-alpha production and NF-KB activation. Additionally, in mouse macrophages, LPS increased the mRNA for smTLR4, Taken together, our results indicate that smTLR4 may function as a feedback mechanism to inhibit the excessive LPS responses in mouse macrophages.