Work

Targeting HMGB1 in endothelial cells reverses heme-induced SIRS after radiofrequency ablation of hepatic hemangioma

Year: 2025

Type: article

Abstract: Background Although radiofrequency ablation (RFA) is a safe and effective treatment for hepatic hemangiomas, post-RFA systemic inflammatory response syndrome (SIRS) frequently occurs. The role of high-mobility group box 1 (HMGB1) in endothelial cell pyroptosis and SIRS induction following RFA in hepatic hemangiomas remains unexplored. Methods In vitro , the levels of interleukin (IL)-1β, IL-18, and pyroptosis markers, such as GSDMD-N and Casp1 p20, were measured in human umbilical vein endothelial cells (HUVECs) after heme administration. In vivo , an orthotopic liver hemangioma mouse model was established, and RFA was performed to evaluate the levels of IL-1β and IL-18, wet-to-dry lung ratio, and inflammation score. In addition, hemopexin and glycyrrhizin were used to investigate the impact of HMGB1 on heme-induced SIRS post-RFA in hepatic hemangioma mice. Results Heme induced elevated levels of IL-1β and IL-18, endothelial cell death in vitro , and increased wet-to-dry lung ratio and inflammation score in vivo . These effects were rescued with the administration of heme-binding protein hemopexin, indicating the role of heme in inducing SIRS and pyroptosis post-RFA of hepatic hemangioma. HMGB1 participates in heme-induced SIRS in mice by regulating HMGB1/nod-like receptor family pyrin domain-containing 3 (NLRP3) pathway through reactive oxygen species (ROS). Treatment with hemopexin or the HMGB1 inhibitor glycyrrhizin reversed heme-induced SIRS after RFA of hepatic hemangioma in mice. Conclusions Collectively, we demonstrated that heme induces SIRS through the ROS/HMGB1/NLRP3 pathway-regulated endothelial cell pyroptosis in mice, and hemopexin, a heme scavenger, and glycyrrhizin, a HMGB1 inhibitor, may be the potential strategies for further study for SIRS following the RFA of hepatic hemangioma for the first time.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2025.1680433