Burn-induced acute lung injury requires a functional Toll-like receptor 4

Shock. 2011 Jul;36(1):24-9. doi: 10.1097/SHK.0b013e318212276b.

Abstract

The role of the Toll-like receptor 4 (TLR4), a component of the innate immune system, in the development of burn-induced acute lung injury (ALI) has not been completely defined. Recent data suggested that an intact TLR4 plays a major role in the development of organ injury in sterile inflammation. We hypothesized that burn-induced ALI is a TLR4-dependent process. Male C57BL/6J (TLR4 wild-type [WT]) and C57BL/10ScN (TLR4 knockout [KO]) mice were subjected to a 30% total body surface area steam burn. Animals were killed at 6 and 24 h after the insult. Lung specimens were harvested for histological examination after hematoxylin-eosin staining. In addition, lung myeloperoxidase (MPO) and intercellular adhesion molecule 1 immunostaining was performed. Lung MPO was measured by an enzymatic assay. Total lung keratinocyte-derived chemoattractant (IL-8) content was measured by enzyme-linked immunosorbent assay. Western blot was performed to quantify phosphorylated IκBα, phosphorylated nuclear factor κB p65 (NF-κBp65), and high mobility group box 1 expression. Acute lung injury, characterized by thickening of the alveolar-capillary membrane, hyaline membrane formation, intraalveolar hemorrhage, and neutrophil infiltration, was seen in WT but not KO animals at 24 h. Myeloperoxidase and intercellular adhesion molecule 1 immunostaining of KO animals was also similar to sham but elevated in WT animals. In addition, a reduction in MPO enzymatic activity was observed in KO mice as well as a reduction in IL-8 levels compared with their WT counterparts. Burn-induced ALI develops within 24 h after the initial thermal insult in our model. Toll-like receptor 4 KO animals were clearly protected and had a much less severe lung injury. Our data suggest that burn-induced ALI is a TLR4-dependent process.

MeSH terms

  • Acute Lung Injury / metabolism*
  • Animals
  • Blotting, Western
  • Burns / metabolism*
  • Burns / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • High Mobility Group Proteins / metabolism
  • I-kappa B Proteins / metabolism
  • Intercellular Adhesion Molecule-1
  • Interleukin-8 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-KappaB Inhibitor alpha
  • Peroxidase / metabolism
  • Toll-Like Receptor 4 / metabolism*
  • Transcription Factor RelA / metabolism

Substances

  • High Mobility Group Proteins
  • I-kappa B Proteins
  • Interleukin-8
  • Nfkbia protein, mouse
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha
  • Peroxidase