Expression of toll-like receptor 2 and 4 is increased in the respiratory epithelial cells of chronic idiopathic interstitial pneumonia patients

Respir Med. 2014 May;108(5):783-92. doi: 10.1016/j.rmed.2013.12.007. Epub 2014 Jan 22.

Abstract

Background: Idiopathic interstitial pneumonia (IIP) is characterized by chronic interstitial inflammation and fibrosis. Although mounting evidence has suggested that toll-like receptor (TLR) 2 and TLR4 are involved in the pathogenesis of non-infectious lung injury in vitro and in mouse models, their roles in human IIP remain unknown.

Methods: To address this issue, we investigated the expression patterns of TLR2 and TLR4 by immunohistochemistry in resected lung tissues from patients with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP).

Results: Type II pneumocytes, bronchial epithelial cells (BECs), and alveolar macrophages accounted for the majority of TLR2- and TLR4-expressing cells in both UIP and NSIP. The numbers of TLR2 and TLR4-positive respiratory epithelial (RE) cells, including type II pneumocytes and BECs, were significantly greater in UIP and NSIP than in the control. In particular, the numbers of TLR2-positive RE cells were much greater in UIP than in NSIP. The intensities of TLR2 and TLR4 expression in type II pneumocytes were also significantly stronger in UIP and NSIP than in the control. A comparison of the TLR expression patterns between the fibroblastic and fibrotic areas in UIP indicated that the numbers TLR2 and TLR4-positive RE cells were similar in fibroblastic areas, whereas the TLR2-positive RE cells outnumbered the TLR4-positive RE cells in the fibrotic areas.

Conclusions: This study demonstrates that RE cells over-express TLR2 and TLR4 in the lungs of IIP patients. These findings suggest that high expression of TLRs may contribute to the pathogenesis of human IIP.

Keywords: Bronchial epithelial cell; NSIP; TLR2; TLR4; Type II pneumocyte; UIP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alveolar Epithelial Cells / metabolism
  • Chronic Disease
  • Epithelial Cells / metabolism
  • Female
  • Fibroblasts / metabolism
  • Humans
  • Idiopathic Interstitial Pneumonias / metabolism*
  • Idiopathic Interstitial Pneumonias / pathology
  • Idiopathic Interstitial Pneumonias / surgery
  • Macrophages, Alveolar / metabolism
  • Male
  • Middle Aged
  • Pulmonary Fibrosis / metabolism
  • Respiratory Mucosa / metabolism*
  • Respiratory Mucosa / pathology
  • Toll-Like Receptor 2 / metabolism*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4