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

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.

journal_name

Int J Chron Obstruct Pulmon Dis

journal_title

International journal of chronic obstructive pulmonary disease

authors

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

doi

10.2147/COPD.S108919

subject

Has Abstract

pub_date

2016-07-28 00:00:00

pages

1705-12

eissn

1176-9106

issn

1178-2005

pii

copd-11-1705

journal_volume

11

pub_type

杂志文章

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