Cutting edge: Differential inhibition of TLR signaling pathways by cell-permeable peptides representing BB loops of TLRs
Cutting edge: Differential inhibition of TLR signaling pathways by cell-permeable peptides representing BB loops of TLRs
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DOI：
10.4049/jimmunol.178.5.2655
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Vogel, Stefanie N.
中科院分区：
文献类型：
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作者：
Toshchakov, Vladimir Y.;Fenton, Matthew J.;Vogel, Stefanie N.
我们设计了由果蝇触角同源域的易位片段与 TLR2、TLR4 和 TLR1/6 的 BB 环序列融合组成的细胞穿透肽。TLR2-和 TLR4-BB 肽 (BBP) 抑制 LPS 诱导的 NF-κ B 易位和早期 IL-1 β mRNA 表达，以及脂肽S-[2,3-双(棕榈酰氧基)-(2-RS)-丙基]-N-棕榈酰基-(R)-Cys-Ser-Lys(4)-OH (P3C)和S-[2,3-双(棕榈酰氧基)-(2-RS)-丙基]-CysSer-Lys(4)-OH(P2C)。 TLR4-和TLR2-BBP 也强烈抑制LPS 诱导的ERK 激活。只有 TLR2-BBP 显着抑制 P3C 诱导的 ERK 激活，P3C 通过 TLR2/1 异二聚体发挥作用。 BBP 不会抑制 M2/6 激动剂 P2C 诱导的 ERK 激活。 TLR2-BBP 诱导 p38 的微弱激活，但不诱导 ERK 或细胞因子 mRNA 的激活。 TLR1/6-BBP 未能抑制任何激动剂诱导的 NF-κB 或 MAPK 激活。我们的结果表明，受体 BBP 选择性地影响不同的 TLR 信号通路，并且 TLR1/6 和 TLR2 的 BB 环在受体异二聚体的形成和接头蛋白的募集中发挥着不同的作用。
We designed cell-penetrating peptides comprised of the translocating segment of Drosophila antennapedia homeodomain fused with BB loop sequences of TLR2, TLR4, and TLR1/6 TLR2- and TLR4-BB peptides (BBPs) inhibited NF-kappa B translocation and early IL-1 beta mRNA expression induced by LPS, and the lipopeptides S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-Cys-Ser-Lys(4)-OH (P3C) and S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-CysSer-Lys(4)-OH (P2C). TLR4- and TLR2-BBPs also strongly inhibited LPS-induced-activation of ERK. Only TLR2-BBP significantly inhibited ERK activation induced by P3C, which acts via TLR2/1 heterodimers. BBPs did not inhibit activation of ERK induced by P2C, a M2/6agonist. The TLR2-BBP induced weak activation of p38, but not ERK or cytokine mRNA. The TLR1/6-BBP failed to inhibit NF-kappa B or MAPK activation induced by any agonist. Our results suggest that the receptor BBPs selectively affect different TLR sionaling pathways, and that the BB loops of TLR1/6 and TLR2 play distinct roles in formation of receptor heterodimers and recruitment ofadaptor proteins.