The role of Toll-like receptors in non-infectious lung injury

在病原体识别的像使用费的受体(TLR ) 的角色在最近的年里是快速地先进的。然而，进在非传染的织物损害的 TLR 的功能的调查刚开始了。以前，我们和其它表明了那碎裂的 hyaluronan (哈) 在织物损害期间积累。CD44 被要求在织物损害期间清除 HA，并且损害了清理哈在不停的发炎的结果。另外，碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近，我们识别了那哈碎片要求 TLR2 和 TLR4 刺激老鼠巨噬细胞生产煽动性的 chemokines 和 cytokines。在一个非传染的肺损害模型，在 TLR2 和 TLR4 缺乏的老鼠显示出煽动性的房间的损害 transepithelial 迁居，增加的织物损害，提高的肺上皮的房间 apoptosis，和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和 apoptosis 的保护的老鼠，部分地通过 NF-kappaB 的 TLR 依赖的基础激活。在 TLR2 和 TLR4 的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害 HA-TLR 相互作用。这些研究识别那个主机矩阵部件哈并且 TLR 相互作用提供开始煽动性的回答的信号，维持上皮的房间完整，并且支持从尖锐的肺损害的恢复。房间研究(2006 ) 16：693-701。做 i：10.1038/sj .cr.7310085；出版联机 2006 年 8 月 8 日。

The role of Toll-like receptors （TLRs） in pathogen recognition has been expeditiously advanced in recent years. However, investigations into the function of TLRs in non-infectious tissue injury have just begun. Previously, we and others have demonstrated that fragmented hyaluronan （HA） accumulates during tissue injury. CD44 is required to clear HA during tissue injury, and impaired clearance of HA results in unremitting inflammation. Additionally, fragmented HA stimulates the expression of inflammatory genes by inflammatory cells at the injury site. Recently, we identified that HA fragments require both TLR2 and TLR4 to stimulate mouse macrophages to produce inflammatory chemokines and cytokines. In a non-infectious lung injury model, mice deficient in both TLR2 and TLR4 show an impaired transepithelial migration of inflammatory cells, increased tissue injury, elevated lung epithelial cell apoptosis, and decreased survival. Lung epithelial cell overexpression of high molecular mass HA protected mice against acute lung injury and apoptosis, in part through TLR-dependent basal activation of NF-κB. The exaggerated injury in TLR2 and TLR4 deficient mice appears to be due to impaired HA-TLR interactions on epithelial cells. These studies identify that host matrix component HA and TLR interactions provide signals that initiate inflammatory responses, maintain epithelial cell integrity, and promote recovery from acute lung injury.