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J Immunol.:我国科学家发现清道夫受体在炎症反应中的功能

  1. 清道夫受体
  2. 炎症反应

来源:浙江大学生命科学院 2012-11-18 18:23

清道夫受体(Scavenger receptor, SR)是模式识别受体家族的重要成员,具有广泛的免疫生物学功能并参与多种疾病的发生,其中对SR在炎症反应中的功能机制是长期来备受关注的热点科学问题。 该研究选择拥有复杂先天免疫系统的鱼类实验模型,发现清道夫受体在病原诱导的炎症反应中发挥重要的负调节功能,揭示了该受体可通过竞争性招募TRAF2信号蛋白以抑制TNF-a炎症信号通路的新机制。

清道夫受体(Scavenger receptor, SR)是模式识别受体家族的重要成员,具有广泛的免疫生物学功能并参与多种疾病的发生,其中对SR在炎症反应中的功能机制是长期来备受关注的热点科学问题。

该研究选择拥有复杂先天免疫系统的鱼类实验模型,发现清道夫受体在病原诱导的炎症反应中发挥重要的负调节功能,揭示了该受体可通过竞争性招募TRAF2信号蛋白以抑制TNF-a炎症信号通路的新机制。

表明不同的天然免疫受体及其介导的信号通路间存在交叉的相互调控作用,这对全面理解炎症信号的网络调控机制与规律提供了新的科学依据。(生物谷Bioon.com)

Scavenger Receptor in Fish Is a Lipopolysaccharide Recognition Molecule Involved in Negative Regulation of NF-κB Activation by Competing with TNF Receptor-Associated Factor 2 Recruitment into the TNF-α Signaling Pathway

Zhen Meng, Xiao-Yu Zhang, Jian Guo, Li-Xin Xiang, Jian-Zhong Shao

Scavenger receptors (SRs) play crucial roles in innate immunity by acting as pattern recognition receptors. Although SRs are widely documented in mammals, data on their occurrence and functions in ancient vertebrates are limited. In this study, we report, to our knowledge, the first cloning and functional characterization of an SR molecule from teleost fish (Tetraodon nigroviridis). This SR (TnSR) was identified as a homolog to mammalian scavenger receptor class A member 5 with the conserved structure of a class A SR. TnSR contained multidomains in a type II transmembrane receptor, including an SR cysteine-rich domain, two coiled-coil collagenous domains, a transmmebrane domain, and a short N-terminal intracellular region with an unexpected TNFR-associated factor 2-binding consensus motif similar to that in human MSR molecules. Phylogenetic analysis suggested that TnSR may be an ancient member of class A SRs resulting from the close relationship between scavenger receptor class A member 5 and macrophage SR in vertebrates associated with the subtle differences in TnSR structure. Subcellular localization analysis showed that TnSR was a cell membrane receptor with homotrimer forms involved in the recognition and internalization of LPS from surface membranes into lysosomes. Functionally, TnSR expression was dramatically induced by LPS stimulation. TnSR served as a negative regulator in LPS-induced NF-κB activation by the competitive recruitment of TNFR-associated factor 2 from the TNF-α signaling pathway. To our knowledge, this is the first report showing that SR plays an inhibitory role in LPS-elicited inflammation by cross-talking with the TNF-α inflammatory pathway. These findings contribute to a better understanding of the biological and evolutionary history of the SR family.

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