TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages.
TLR4, but not TLR2, mediates IFN-beta-induced STAT1alpha/beta-dependent gene expression in macrophages.
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DOI：
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发表时间：
2002
影响因子：
30.5
通讯作者：
Vladimir Toshchakov;Bryan W. Jones;P. Perera;K. Thomas;M. J. Cody;Shuling Zhang;B. Williams;J. Major;T. Hamilton;M. Fenton;S. Vogel
中科院分区：
文献类型：
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作者：
Vladimir Toshchakov;Bryan W. Jones;P. Perera;K. Thomas;M. J. Cody;Shuling Zhang;B. Williams;J. Major;T. Hamilton;M. Fenton;S. Vogel
Toll样受体2（TLR 2）激动剂诱导TLR 4诱导的促炎基因的子集，这表明使用差异信号传导途径。用TLR 4激动剂大肠杆菌脂多糖（LPS）刺激而不是用TLR 2激动剂刺激的小鼠巨噬细胞诱导信号转导和转录激活因子1 α（STAT 1 α）和STAT 1 β的磷酸化，这被干扰素β（IFN-β）抗体阻断，但不被IFN-α阻断。所有TLR 2激动剂都很难诱导IFN-β，IFN-β由立即早期LPS诱导基因编码。因此，TLR 2激动剂诱导STAT 1依赖性基因的失败部分是由于它们不能表达IFN-β。TLR 4诱导的IFN-β mRNA不依赖于MyD 88和PKR（双链RNA依赖性蛋白激酶），但依赖于TIRAP（Toll-白细胞介素1受体结构域的衔接蛋白）。总之，这些发现为TLR 4和TLR 2激动剂激活的基因表达的差异模式提供了第一个机制基础。
Toll-like receptor 2 (TLR2) agonists induce a subset of TLR4-inducible proinflammatory genes, which suggests the use of differential signaling pathways. Murine macrophages stimulated with the TLR4 agonist Escherichia coli lipopolysaccharide (LPS), but not with TLR2 agonists, induced phosphorylation of signal transducer and activator of transcription 1alpha (STAT1alpha) and STAT1beta, which was blocked by antibodies to interferon beta (IFN-beta) but not IFN-alpha. All TLR2 agonists poorly induced IFN-beta, which is encoded by an immediate early LPS-inducible gene. Thus, the failure of TLR2 agonists to induce STAT1-dependent genes resulted, in part, from their inability to express IFN-beta. TLR4-induced IFN-beta mRNA was MyD88- and PKR (double-stranded RNA-dependent protein kinase)-independent, but TIRAP (Toll-interleukin 1 receptor domain-containing adapter protein)-dependent. Together, these findings provide the first mechanistic basis for differential patterns of gene expression activated by TLR4 and TLR2 agonists.