Induction of high-mobility group Box-1 in vitro and in vivo by respiratory syncytial virus

Background Despite decades that have passed since its discovery, accurate biomarkers of respiratory syncytial virus (RSV) disease activity and effective therapeutic strategies are still lacking. The high-mobility group box type 1 (HMGB1) protein has been proposed as a possible link between RSV and i...

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Bibliographic Details
Published in:Pediatric research 2018-05, Vol.83 (5), p.1049-1056
Main Authors: Manti, Sara, Harford, Terri J, Salpietro, Carmelo, Rezaee, Fariba, Piedimonte, Giovanni
Format: Article
Language:English
Subjects:
Animals
basic-science-investigation
Biomarkers
Biomarkers - metabolism
Bronchi - metabolism
Bronchiolitis - virology
Cell Line
Epithelial Cells - metabolism
Gene Expression Profiling
HMGB1 Protein - metabolism
Humans
Immune System
Infections
Lung - metabolism
Medicine
Medicine & Public Health
Pediatric Surgery
Pediatrics
Rats
Rats, Inbred F344
Respiratory syncytial virus
Respiratory Syncytial Virus Infections - metabolism
Respiratory Syncytial Viruses - metabolism
Respiratory Tract Infections - metabolism
Respiratory Tract Infections - virology
Up-Regulation
Virus Replication
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Summary:Background Despite decades that have passed since its discovery, accurate biomarkers of respiratory syncytial virus (RSV) disease activity and effective therapeutic strategies are still lacking. The high-mobility group box type 1 (HMGB1) protein has been proposed as a possible link between RSV and immune system, but only limited information is currently available to support this hypothesis. Methods Expression of HMGB1 gene and protein was analyzed by quantitative PCR, enzyme-linked immunosorbent assay (ELISA), western blot, immunocytochemistry, and confocal microscopy in immortalized and primary human bronchial epithelial cells, as well as in rat pup lungs. The role of HMGB1 in RSV infection was explored using glycyrrhizin, a selective HMGB1 inhibitor. Results RSV infection strongly induced HMGB1 expression both in vitro and in vivo . Glycyrrhizin dose-dependently inhibited HMGB1 upregulation in both RSV-infected immortalized and primary human bronchial epithelial cells, and this effect was associated with significant reduction of viral replication. Conclusion Our data suggest that HMGB1 expression increases during RSV replication. This seems to have a critical pathogenic role as its selective inhibition virtually modified the infection. These observations provide further insight into the pathophysiology of RSV infection and uncover a potential biomarker and therapeutic target for the most common respiratory infection of infancy.
ISSN:0031-3998
1530-0447
DOI:10.1038/pr.2018.6