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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Inflammation 1/2017

Depletion of club cells attenuates bleomycin-induced lung injury and fibrosis in mice

Zeitschrift:
Journal of Inflammation > Ausgabe 1/2017
Autoren:
Tetsuya Yokoyama, Toyoshi Yanagihara, Kunihiro Suzuki, Naoki Hamada, Kazuya Tsubouchi, Saiko Ogata-Suetsugu, Hironori Mikumo, Chika Ikeda-Harada, Takashige Maeyama, Kazuyoshi Kuwano, Yoichi Nakanishi

Abstract

Background

The role of bronchiolar epithelial cells in the pathogenesis of pulmonary fibrosis has not been clarified. We previously demonstrated DNA damage in murine bronchioles in the early stages of bleomycin-induced pulmonary fibrosis that subsequently extended to alveolar cells at the advanced stages of the disease. Club cells are progenitor cells for bronchioles and are known to play protective roles against lung inflammation and damage. The aim of the present study was to elucidate the role of club cells in the development of pulmonary fibrosis.

Methods

C57BL/6 J mice received naphthalene intraperitoneally on day −2 to deplete club cells and were given intratracheal bleomycin or a vehicle on day 0. Lung tissues were obtained on days 1, 7, and 14, and bronchoalveolar lavage was performed on day 14. Bronchiolar epithelial cells sampled by laser capture microdissection were analyzed by gene expression microarray analysis on day 14.

Results

Club cell depletion induced by naphthalene protected mice from bleomycin-induced lung injury and fibrosis. Bleomycin-triggered bronchiolar TGF-β1 expression was reduced. Gene expression microarray analysis revealed that genes associated with inflammatory response and chemokine activity were downregulated in the bleomycin-injured bronchiolar epithelium with club cell injury compared to that in bronchiolar epithelium without cell injury.

Conclusions

Club cells are involved in the development of lung injury and fibrosis.
Literatur
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