{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T11:35:39Z","timestamp":1762428939849,"version":"build-2065373602"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      , the levels of interleukin (IL)-1\u03b2, IL-18, and pyroptosis markers, such as GSDMD-N and Casp1 p20, were measured in human umbilical vein endothelial cells (HUVECs) after heme administration.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , an orthotopic liver hemangioma mouse model was established, and RFA was performed to evaluate the levels of IL-1\u03b2 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Heme induced elevated levels of IL-1\u03b2 and IL-18, endothelial cell death\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and increased wet-to-dry lung ratio and inflammation score\n                      <jats:italic>in vivo<\/jats:italic>\n                      . 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1680433","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T05:29:36Z","timestamp":1762406976000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting HMGB1 in endothelial cells 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