Critical role of tumor necrosis factor receptor 1 in the pathogenesis of pulmonary emphysema in mice

Masaki Fujita, Hiroshi Ouchi, Satoshi Ikegame, Eiji Harada, Takemasa Matsumoto, Junji Uchino, Yoichi Nakanishi, Kentaro Watanabe

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Abstract

COPD is a major cause of chronic morbidity and mortality throughout the world. Although tumor necrosis factor-α (TNF-α) has a critical role in the development of COPD, the role of different TNF receptors (TNFRs) in pulmonary emphysema has not been resolved. We aimed to clarify the role of TNFRs in the development of pulmonary emphysema. TNF-α transgenic mice, a murine model of COPD in which the mice spontaneously develop emphysema with a large increase in lung volume and pulmonary hypertension, were crossed with either TNFR1-deficient mice or TNFR2-deficient mice. After 6months, the gross appearance of the lung, lung histology, and pulmonary and cardiac physiology were determined. In addition, the relationship between apoptosis and emphysema was investigated. Pulmonary emphysema-like changes disappeared with deletion of TNFR1. However, slight improvements were attained with deletion of TNFR2. Apoptotic cells in the interstitium of the lung were observed in TNF-α transgenic mice. The apoptotic signals through TNFR1 appear critical for the pathogenesis of pulmonary emphysema. In contrast, the inflammatory process has a less important role for the development of emphysema.

Original languageEnglish
Pages (from-to)1705-1712
Number of pages8
JournalInternational Journal of COPD
Volume11
Issue number1
DOIs
Publication statusPublished - Jul 28 2016

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All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Health Policy
  • Public Health, Environmental and Occupational Health

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