Protective effects of anti-HMGB1 monoclonal antibody on lung ischemia reperfusion injury in mice
Protective effects of anti-HMGB1 monoclonal antibody on lung ischemia reperfusion injury in mice
复制标题
DOI：
10.1016/j.bbrc.2021.08.015
复制
发表时间：
2021-08-18
影响因子：
3.1
通讯作者：
Toyooka, Shinichi
中科院分区：
文献类型：
--
作者：
Nakata, Kentaro;Okazaki, Mikio;Toyooka, Shinichi
在缺血再灌注(IR)损伤中，高迁移率族蛋白1(HMGB1)是一种染色质结合蛋白，从坏死细胞中释放出来，并触发炎症反应。我们评价了中和性抗HMGB1单抗对肺IR损伤的治疗作用。采用小鼠肝门部缺血再灌注模型，随机分为假手术组和缺血再灌注组，分别静脉注射抗HMGB 1单抗和对照单抗。通过检测肺组织氧合、肺损伤评分、中性粒细胞浸润、促炎症细胞因子和趋化因子表达、丝裂原活化蛋白激酶(MAPK)信号转导水平和细胞凋亡率，分析抗HMGB1单抗抗IR损伤的作用。抗HMGB1单抗可显著降低IR升高的血浆HMGB1水平。抗HMGB1单抗治疗可明显改善IR损伤的严重程度，包括氧合能力、肺损伤评分和中性粒细胞浸润。IL-1β、IL-6、IL-12、肿瘤坏死因子-α、CXCL-1和CXCL-2等促炎因子的表达和p38MAPK的磷酸化均显著降低。此外，通过TUNEL检测，抗HMGB1单抗治疗抑制了细胞凋亡。总体而言，抗HMGB1单抗通过减少炎症反应和细胞凋亡而改善肺IR损伤。我们的研究结果表明，抗HMGB1单抗有可能用于改善肺移植中的IR损伤症状。(C)爱思唯尔公司出版的《2021年》。
During ischemia reperfusion (IR) injury, high mobility group box 1 (HMGB1), a chromatin binding protein, is released from necrotic cells and triggers inflammatory responses. We assessed the therapeutic effect of a neutralizing anti-HMGB1 monoclonal antibody (mAb) on lung IR injury. A murine hilar clamp model of IR was used, where mice were divided into sham and IR groups with intravenous administration of anti-HMGB 1 mAb or control mAb. We analyzed the effect of anti-HMGB1 mAb against IR injury by assessing lung oxygenation, lung injury score, neutrophil infiltration, expression of proinflammatory cytokines and chemokines, levels of mitogen-activated protein kinase (MAPK) signaling, and measurement of apoptotic cells. Anti-HMGB1 mAb significantly decreased the plasma level of HMGB1 elevated by IR. The severity of IR injury represented by oxygenation capacity, lung injury score, and neutrophil infiltration was significantly improved by anti-HMGB1 mAb treatment. The expression of proinflammatory factors, including IL-1 beta, IL-6, IL-12, TNF-alpha, CXCL-1, and CXCL-2, and phosphorylation of p38 MAPK were both significantly reduced by anti-HMGB1 mAb treatment. Furthermore, anti-HMGB1 mAb treatment suppressed apoptosis, as determined through TUNEL assays.Overall, anti-HMGB1 mAb ameliorated lung IR injury by reducing inflammatory responses and apoptosis. Our findings indicate that anti-HMGB1 mAb has potential for use as a therapeutic to improve IR injury symptoms during lung transplantation. (C) 2021 Published by Elsevier Inc.