IL-1RⅠ/MyD88-TIR mimic AS-1 inhibits the activation of MyD88-dependent signaling pathway induced by IL-1β in vitro
Yulong Hu
Ting Li
Yong mei Wang
Lin Guo
Xiaohong Shan
Jing Li
Qi Chen
Yuehua Li
摘要：Objective:To test whether IL-1 RⅠ/My088-TIR mimic AS-1 can work as a new compound that targeted at blocking MyD88-dependent signaling pathway,we investigated the physical structure and biological function of AS-1.Methods:The crystallographic structure of AS-1 was examined by 1H nuclear magnetic resonance.The toxicity of AS-1 was measured with Methyl thiazolyl tetrazolium (MTT)assay.The effect of AS-1 on phosphorylation state of p38 MAPK and IRAK-1 was observed with Western blot.Results:The crystallographic details of AS-1 demonstrated that it was a tri-peptide sequence[(F/Y)-(V/L/I)-(P/G)]of the IL-1R Ⅰ-TIR domain BBloop.No toxicity of AS-1 was shown to HEK 293A cells.The phosphorylation of p38 MAPK,induced by IL-1β significantly increased from those in the control group.AS-1 significantly reduced the phosphorylation of p38 MAPK induced by IL-1β.IL-1 β increased the phosphorylation of IRAK-1 significantly.which Was prevented by AS-1.Conclusion:AS-1 is a competitive mimic between IL-1R Ⅰ-TIR and MyD88-TIR domain,which most likely interferes with MyD88-dependent signaling pathway.
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分类号：R3(基础医学)
资助基金：国家自然科学基金(30571842)
论文发表日期：2007-11-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：5( 354-358 )
英文信息