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 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 immorta lized 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 piovide further insight into the pathophysiology of RSV infection and uncover a potential biomarker and therapeutic target for the most common respiratory infection of infancy.