Regulation of lung injury and repair by Toll-like receptors and hyaluronan.

Published

Journal Article

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-kappaB. Hyaluronan-TLR2 and hyaluronan-TLR4 interactions provide signals that initiate inflammatory responses, maintain epithelial cell integrity and promote recovery from acute lung injury.

Full Text

Cited Authors

  • Jiang, D; Liang, J; Fan, J; Yu, S; Chen, S; Luo, Y; Prestwich, GD; Mascarenhas, MM; Garg, HG; Quinn, DA; Homer, RJ; Goldstein, DR; Bucala, R; Lee, PJ; Medzhitov, R; Noble, PW

Published Date

  • November 2005

Published In

Volume / Issue

  • 11 / 11

Start / End Page

  • 1173 - 1179

PubMed ID

  • 16244651

Pubmed Central ID

  • 16244651

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm1315

Language

  • eng