Toll-like receptor signaling stimulates cell cycle entry and progression in fibroblasts
Toll-like receptor signaling stimulates cell cycle entry and progression in fibroblasts
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DOI：
10.1074/jbc.m500877200
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发表时间：
2005-05-27
影响因子：
4.8
通讯作者：
Vlach, J
中科院分区：
文献类型：
--
作者：
Hasan, UA;Trinchieri, G;Vlach, J
toll样受体（TLRs）是一种参与识别外来病原体相关分子模式和激活导致先天免疫识别过程的蛋白质。我们发现，用TLR5配体鞭毛蛋白刺激成纤维细胞，可以诱导血清饥饿细胞的增殖，或在血清退出后阻止细胞周期退出，而不依赖于自体生长因子的分泌。其他TLR配体，如poly（I:C）和脂多糖，只有在I型干扰素的作用被阻断时才能产生类似的效果。鞭毛蛋白刺激可以防止外源性周期蛋白依赖性激酶抑制剂p27过表达引起的细胞周期阻滞。刺激TLR5和MyD88过表达，而不是TRIF、TIRAP或TRAM，会导致p27降解，这可以通过显性负Akt和p27 c端Thr（187）位点突变来抑制。这些数据为TLR信号的非免疫和细胞自主作用提供了证据，因此TLR刺激为细胞分裂提供了积极信号。
Toll-like receptors (TLRs) are proteins involved in recognition of foreign pathogen-associated molecular patterns and activation of processes leading to innate immune recognition. We show that stimulation of fibroblasts with a TLR5 ligand, flagellin, can induce proliferation of serum-starved cells or prevent cell cycle exit upon serum withdrawal independently of autologous growth factor secretion. Other TLR ligands, such as poly(I:C) and lipopolysaccharide, can have a similar effect only if the action of type I interferons is blocked. Flagellin stimulation can prevent cell cycle arrest induced by overexpression of exogenous cyclin-dependent kinase inhibitor p27. Stimulation of TLR5 and overexpression of MyD88, but not TRIF, TIRAP, or TRAM, result in p27 degradation, which can be suppressed by dominant negative Akt and mutation of the p27 C-terminal Thr(187) site. These data provide evidence for a nonimmune and cell autonomous role of TLR signaling, whereby TLR stimulation provides a positive signal for cell division.