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IL-17A contributes to HSV1 infection-induced acute lung injury in a mouse model of pulmonary fibrosis.


ABSTRACT: BACKGROUND:Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold. AIMS:To establish a mouse model of virus infection-induced AE-IPF and investigate the mechanism underlying the AE-IPF. METHODS:Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild-type (WT) and IL-17A gene knockout (IL-17A-/- ) mice 21 days after intratracheal administration of bleomycin (BLM). RESULTS:HSV1 infection caused acute exacerbation in mice with BLM-induced fibrosis. Compared with the BLM+Saline mice, the mice with BLM+HSV1 showed significantly higher acute lung injury (ALI) score (P < 0.0001), lower survival rate (100% vs 21.4%, P < 0.0001), poorer lung function and higher inflammatory response representing by increased total inflammatory cells in bronchoalveolar lavage fluid (BALF) (P = 0.0323), increased proportion of Th17 cells in peripheral blood (P = 0.0004) and higher inflammatory factors in BALF. In addition, HSV1 infection increased the expression of endoplasmic reticulum stress (ERS)-related proteins in mice with BLM-induced fibrosis. The inhibition of ERS by tauroursodeoxycholic acid (TUDCA, an ERS inhibitor) significantly reduced the IL-17A levels in BALF (P = 0.0140) and TH17 cells in the peripheral blood (P = 0.0084) of mice with BLM+HSV1, suggesting that suppression of ERS may reduce TH17 response in mice with AE-IPF. Compared with WT mice with BLM+HSV1, IL-17A-/- mice with BLM+HSV1 had lower ALI score (P = 0.0119), higher survival rate (78.6% vs 21.4%, P = 0.004), improved lung function, and milder inflammatory response. CONCLUSIONS:HSV1 infection in addition to BLM-induced IPF can successfully establish AE-IPF in mice. IL-17A and ERS promote lung inflammation in AE-IPF development.

SUBMITTER: Chen T 

PROVIDER: S-EPMC6349191 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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IL-17A contributes to HSV1 infection-induced acute lung injury in a mouse model of pulmonary fibrosis.

Chen Tao T   Qiu Hui H   Zhao Meng-Meng MM   Chen Shan-Shan SS   Wu Qin Q   Zhou Nian-Yu NY   Lu Li-Qin LQ   Song Jia-Cui JC   Tang Dan-Li DL   Weng Dong D   Li Hui-Ping HP  

Journal of cellular and molecular medicine 20181030 2


<h4>Background</h4>Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold.<h4>Aims</h4>To establish a mouse model of virus infection-induced AE-IPF and investigate the mechanism underlying the AE-IPF.<h4>Methods</h4>Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild-type (WT) and IL-17A gene knockout (IL-17A<sup>-/-</sup> ) mice 21 days after intratracheal administration of bleomycin (BLM).<h4>Results</h4>HSV1 inf  ...[more]

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