Saha Sukumar, Qi Jin, Wang Shiyong, Wang Minhui, Li Xinna, Kim Yun-Gi, Núñez Gabriel, Gupta Dipika, Dziarski Roman
Indiana University School of Medicine Northwest, Gary, IN 46408, USA.
Cell Host Microbe. 2009 Feb 19;5(2):137-50. doi: 10.1016/j.chom.2008.12.010.
Peptidoglycan recognition proteins (PGRPs) are structurally conserved from insects to mammals. Insect PGRPs have diverse host-defense functions. Mammalian PGRPs PGLYRP-1, PGLYRP-3, and PGLYRP-4 have bactericidal activity, while PGLYRP-2 has amidase activity. To extend the known functions of mammalian PGRPs, we examined whether they have immunomodulating activities in peptidoglycan-induced arthritis in mice. We demonstrate that PGLYRP-2 and Nod2 are both required for arthritis in this model. 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. Only PGLYRP-2 among the four mammalian PGRPs displays this proinflammatory function, and PGLYRP-1 is anti-inflammatory. Toll-like receptor 4 (TLR4) and MyD88 are required for maturation of neutrophils before peptidoglycan challenge. Our results demonstrate that PGRPs, Nod2, and TLR4, representing three different types of pattern-recognition molecules, play interdependent in vivo roles in local inflammation.
肽聚糖识别蛋白（PGRPs）在结构上从昆虫到哺乳动物都保持保守。昆虫PGRPs具有多种宿主防御功能。哺乳动物PGRPs中的PGLYRP-1、PGLYRP-3和PGLYRP-4具有杀菌活性，而PGLYRP-2具有酰胺酶活性。为了扩展哺乳动物PGRPs的已知功能，我们研究了它们在小鼠肽聚糖诱导的关节炎中是否具有免疫调节活性。我们证明在该模型中，关节炎的发生PGLYRP-2和Nod2都是必需的。肽聚糖诱导的关节炎中的事件顺序是Nod2激活、PGLYRP-2的局部表达、趋化因子产生以及中性粒细胞募集到四肢，从而诱发急性关节炎。在四种哺乳动物PGRPs中，只有PGLYRP-2表现出这种促炎功能，而PGLYRP-1具有抗炎作用。在肽聚糖攻击之前，Toll样受体4（TLR4）和髓样分化因子88（MyD88）是中性粒细胞成熟所必需的。我们的结果表明，代表三种不同类型模式识别分子的PGRPs、Nod2和TLR4在局部炎症中发挥相互依赖的体内作用。
