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

Authors Fujita M, Ouchi H, Ikemage S, Harada E, Matsumoto T, Uchino J, Nakanishi Y, Watanabe K

Received 21 March 2016

Accepted for publication 7 May 2016

Published 28 July 2016 Volume 2016:11(1) Pages 1705—1712


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Professor Hsiao-Chi Chuang

Peer reviewer comments 3

Editor who approved publication: Dr Richard Russell

Masaki Fujita,1 Hiroshi Ouchi,2 Satoshi Ikegame,2 Eiji Harada,2 Takemasa Matsumoto,1 Junji Uchino,1 Yoichi Nakanishi,2 Kentaro Watanabe1

1Department of Respiratory Medicine, Faculty of Medicine, Fukuoka University, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

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 6 months, 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.

Keywords: TNF-α, receptor, emphysema, apoptosis

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