HMGB1-induced endothelial cell pyroptosis is involved in systemic inflammatory response syndrome following radiofrequency ablation of hepatic hemangiomas.

Abstract:

:The goal of this study was to assess the role of high-mobility group box 1 (HMGB1)-induced endothelial cell (EC) pyroptosis in systemic inflammatory response syndrome (SIRS) following radiofrequency (RF) ablation of hepatic hemangiomas. We enrolled 76 patients with hepatic hemangioma who underwent RF ablation. Serum concentrations of HMGB1, interleukin (IL)-1β, IL-18 and lactate dehydrogenase (LDH) were determined at different time points. Immunohistochemistry staining (IHC) was performed to evaluate the expressions of HMGB1, NLRP3, caspase-1, GSDMD, IL-18 and IL-1β in hepatic hemangioma and sub-ablated hemangioma tissues. In vitro experiments used human umbilical vein endothelial cells (HUVECs) treated with sub-ablative hyperthermia to mimic insufficient RF ablation of hepatic hemangiomas. ELISA and western blotting were performed to quantify HMGB1, NLRP3, caspase-1, GSDMD, IL-18, IL-1β and LDH levels with or without the addition of ethyl pyruvate (EP), a HMGB1 inhibitor, in the medium. Flow cytometry and fluorescent staining were performed to assess pyroptosis of HUVECs. Twenty-nine patients experienced SIRS after RF ablation (29/76, 38.2%). HMGB1, IL-1β and IL-18 levels were significantly correlated with SIRS. IHC staining revealed an obvious increase in HMGB1, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β in the ECs of sub-ablated hemangioma but not in hepatic hemangioma. In vitro experiments showed that subablative hyperthermia led to HMGB1-induced pyroptosis of HUVECs and EP attenuated the pyroptosis of HUVECs. Taken together, these data demonstrate HMGB1-induced ECs pyroptosis may occur during SIRS following RF ablation of hepatic hemangiomas.

journal_name

Am J Transl Res

authors

Yang M,Yang X,Wang S,Xu L,Ke S,Ding X,Sun W,Gao J

subject

Has Abstract

pub_date

2019-12-15 00:00:00

pages

7555-7567

issue

12

issn

1943-8141

journal_volume

11

pub_type

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