PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation.
PGLYRP-2 and Nod2 are both required for peptidoglycan-induced arthritis and local inflammation.
复制标题
DOI：
10.1016/j.chom.2008.12.010
复制
发表时间：
2009-02-19
影响因子：
30.3
通讯作者：
Dziarski R
中科院分区：
文献类型：
--
作者：
Saha S;Qi J;Wang S;Wang M;Li X;Kim YG;Núñez G;Gupta D;Dziarski R
肽聚糖识别蛋白（PGRP）是从昆虫到哺乳动物结构上保守的蛋白。昆虫PGRP具有多种宿主防御功能，而哺乳动物PGRP仅具有杀菌和酰胺酶活性。我们询问哺乳动物PGRP是否在肽聚糖诱导的关节炎中具有免疫调节活性，以及它们是否与其他先天免疫受体相互作用。我们证明了PGLYRP-2和Nod 2都是肽聚糖诱导关节炎所必需的。肽聚糖诱导的关节炎中的事件顺序是Nod 2的激活、PGLYRP-2的局部表达、趋化因子的产生和中性粒细胞向肢体中的募集，这诱导急性关节炎。这种促炎功能对于PGLYRP-2是独特的，并且不被其他PGRP表现出，其中一种（PGLYRP-1）是抗炎的。TLR 4和MyD 88是嗜中性粒细胞在肽聚糖攻击前成熟所必需的。我们的研究结果揭示了PGRP，Nod 2和TLR 4的新的体内功能，并证明了这三种模式识别分子家族在局部炎症中的体内相互依赖性。
Peptidoglycan recognition proteins (PGRPs) are structurally conserved from insects to mammals. Insect PGRPs have many host defense functions, whereas mammalian PGRPs only have bactericidal and amidase activities. We asked whether mammalian PGRPs have immunomodulating activities in peptidoglycan-induced arthritis and whether they interact with other innate immunity receptors. We demonstrate that PGLYRP-2 and Nod2 are both required for induction of arthritis by peptidoglycan. The sequence of events in peptidoglycan-induced arthritis is activation of Nod2, local expression of PGLYRP-2, chemokine production, and recruitment of neutrophils into the limbs, which induces acute arthritis. This proinflammatory function is unique for PGLYRP-2 and is not exhibited by other PGRPs, of which one (PGLYRP-1) is anti-inflammatory. TLR4 and MyD88 are required for maturation of neutrophils before peptidoglycan challenge. Our results reveal new in vivo functions of PGRPs, Nod2, and TLR4, and demonstrate in vivo interdependence of these three families of pattern recognition molecules in local inflammation.
登录
查看更多内容
影响因子：
6.7
作者：
Bischoff V;Vignal C;Duvic B;Boneca IG;Hoffmann JA;Royet J
通讯作者：
Royet J
影响因子：
--
作者：
LEHMAN, TJA;ALLEN, JB;WILDER, RL
通讯作者：
WILDER, RL
影响因子：
4.8
作者：
Liu, C;Gelius, E;Dziarski, R
通讯作者：
Dziarski, R
影响因子：
3.1
作者：
FOX, A;BROWN, RR;SCHWAB, JH
通讯作者：
SCHWAB, JH
影响因子：
4.8
作者：
Girardin, SE;Travassos, LH;Mengin-Lecreulx, D
通讯作者：
Mengin-Lecreulx, D