Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature Medicine 11, 1173 - 1179 (2005)
Published online: 23 October 2005 | doi:10.1038/nm1315
Regulation of lung injury and repair by Toll-like receptors and hyaluronan
Dianhua Jiang1, Jiurong Liang1, Juan Fan1, Shuang Yu1, Suping Chen2, Yi Luo3, Glenn D Prestwich3, Marcella M Mascarenhas4, Hari G Garg4, Deborah A Quinn4, Robert J Homer2, Daniel R Goldstein5, Richard Bucala6, Patty J Lee1, Ruslan Medzhitov7 & Paul W Noble1
Abstract
Mechanisms that regulate inflammation and repair after acute lung injury are incompletely understood. The extracellular matrix glycosaminoglycan hyaluronan is produced after tissue injury and impaired clearance results in unremitting inflammation. Here we report that hyaluronan degradation products require MyD88 and both Toll-like receptor (TLR)4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury. Hyaluronan fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner. Myd88-/- and Tlr4-/-Tlr2-/- mice showed impaired transepithelial migration of inflammatory cells but decreased survival and enhanced epithelial cell apoptosis after lung injury. Lung epithelial cell–specific overexpression of high-molecular-mass hyaluronan was protective against acute lung injury. Furthermore, epithelial cell–surface hyaluronan was protective against apoptosis, in part, through TLR-dependent basal activation of NF-
B. Hyaluronan-TLR2 and hyaluronan-TLR4 interactions provide signals that initiate inflammatory responses, maintain epithelial cell integrity and promote recovery from acute lung injury.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Identification of IGFBP-6 as an effector of the tumor suppressor activity of SEMA3BOncogene Original Article
Manganese Superoxide Dismutase Affects Cytochrome c Release and Caspase-9 Activation After Transient Focal Cerebral Ischemia in MiceJournal of Cerebral Blood Flow & Metabolism Original Article
Experimentally-induced warm renal ischemia induces cortical accumulation of hyaluronan in the kidneyKidney International Original Article
See all 27 matches for Research