Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model

Wang,Lina; Cheng,Wei; Zhang,Zhimin

doi:10.3892/mmr.2017.6558

Respiratory syncytial virus infection accelerates lung fibrosis through the unfolded protein response in a bleomycin-induced pulmonary fibrosis animal model

Authors:
- Lina Wang
- Wei Cheng
- Zhimin Zhang
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Affiliations: Department of Respiratory Diseases, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Respiratory and Intensive Medicine, University of Virginia, Charlottesville, VA 22908, USA
Published online on: May 10, 2017 https://doi.org/10.3892/mmr.2017.6558
Pages: 310-316

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Abstract

Emerging evidence has demonstrated that endoplasmic reticulum stress (ER) is involved in the pathogenesis of idiopathic pulmonary fibrosis, however, the underlying mechanism remains unclear. Viral infection often triggers a hyperinflammatory response by an expansion of the ER. The present study was designed to observe the role of respiratory syncytial virus infection (RSV)‑induced ER stress on lung fibrosis. In order to determine the role of ER stress on the onset and progression of pulmonary fibrosis, mice received an intratracheal combined injection of RSV and bleomycin on day 0. At day 7, 14 and 21 following combined injection, RSV in the lung tissues was assayed by immunohistochemistry, cellular classification was assayed by direct microscopic observation after Wright staining and the secretion of cytokines in the broncho‑alveolar lavage fluid (BALF) was assayed by ELISA. The expression of collagen type I was assayed by immunofluorescence and western blot analysis. The expression of ER stress related proteins was analyzed by western blot. In addition, the correlations of ER‑stress related proteins with collagen type‑1 were examined. RSV administration resulted in increased inflammation, as demonstrated by increased levels of leukocytes and pro‑inflammatory cytokines in the BALF, and increased collagen type‑1 deposition in the lung tissues of bleomycin-induced pulmonary fibrosis animal model at 7, 14 and 21 days. RSV promoted the expression of phosphorylated protein kinase R‑like endoplasmic reticulum kinase (p‑PERK), 78 kDa glucose‑regulated protein (GRP78) and activating transcription factor 6α (ATF6α), which accelerated the severity and process of fibrosis in bleomycin‑induced animal models. The present study provides evidence that RSV infection accelerated the unfolded protein response and bleomycin‑induced lung fibrosis, which may improve our understanding of the pathogenesis of pulmonary fibrosis.

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