taurochenodeoxycholic-acid and Herpes-Simplex

Patients with idiopathic pulmonary fibrosis (IPF) often experience acute exacerbation (AE) after an episode of common cold.. To establish a mouse model of virus infection-induced AE-IPF and investigate the mechanism underlying the AE-IPF.. Herpes simplex virus 1 (HSV1) was inoculated intranasally to wild-type (WT) and IL-17A gene knockout (IL-17A. 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. 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.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antiviral Agents; Bleomycin; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Endoplasmic Reticulum Stress; Gene Expression; Herpes Simplex; Herpesvirus 1, Human; Humans; Idiopathic Pulmonary Fibrosis; Interleukin-17; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Respiratory Function Tests; Survival Analysis; Taurochenodeoxycholic Acid; Th17 Cells