抑制HMGB1可过ROS/ AMPK/自噬通路减轻TDI诱导的职业性哮喘
2023/11/23
摘要
背景：甲苯二异氰酸酯(TDI)暴露可引起哮喘等肺部疾病。抑制高迁移率族蛋白B1(HMGB1)可减轻TDI对人支气管上皮(HBE)细胞的毒性作用。
方法：在这里，我们评估了HMGB1在TDI引起的哮喘小鼠中的体内积极作用，并探索了其在HBE细胞中的潜在机制。
结果：我们发现HMGB1的抑制明显减轻了哮喘小鼠肺组织的气道炎症、气道高反应性和气道重塑。体外实验结果表明，抑制HMGB1可改善TDI诱导的HBE细胞活性氧(ROS)释放、炎症反应和自噬激活。在分子水平上，抑制HMGB1可降低HMGB1、toll样受体4、波形蛋白和基质金属蛋白酶-9蛋白的表达，激活NF-κB和NOD样受体蛋白3 (NLRP3)炎症小体，增加E-钙黏蛋白的表达。重要的是，在TDI诱导的哮喘中，自噬的激活可能导致NLRP3炎症小体的过度激活。
结论;抑制HMGB1可通过ROS/AMPK/自噬途径减轻TDI诱导的哮喘，这可能为TDI诱导的哮喘的发病机制和治疗靶点提供有价值的证据。
Inhibition of HMGB1 alleviates TDI-induced occupational asthma via the ROS/ AMPK/ autophagy pathway
Xiangjing Meng, Sumei Guo, Xiaoxia Zhang et al.
Abstract
BACKGROUND:Exposure to toluene diisocyanate (TDI) can cause pulmonary diseases such as asthma. Inhibition of high mobility group box 1 protein (HMGB1) has been found to be protective against the toxic effects of TDI on human bronchial epithelial (HBE) cells.
METHODS: Here, we evaluated the in vivo positive roles of HMGB1 in the TDI-caused asthma mice and explored its underlying mechanisms in HBE cells.
RESULTS:We found that suppression of HMGB1 obviously alleviated airway inflammation, airway hyperresponsiveness, and airway remodeling in the lung tissue of the asthma mice. The in vitro results showed that inhibition of HMGB1 ameliorated TDI-induced reactive oxygen species (ROS) release, inflammatory response, and activation of autophagy in HBE cells. At the molecular level, inhibition of HMGB1 decreased the expressions of HMGB1, Toll-like receptor 4, Vimentin and matrix metalloproteinase-9 proteins, activated NF-κB and NOD-like receptor protein 3 (NLRP3) inflammasome, and increased E-cadherin expression. Importantly, activation of autophagy could lead to the overactivation of NLRP3 inflammasome in TDI-induced asthma.
CONCLUSIONS: These results suggest that inhibition of HMGB1 can alleviate TDI-induced asthma through ROS/AMPK/autophagy pathways, which may provide valuable evidence for the pathogenesis and therapeutic targets of TDI-induced asthma.
背景：甲苯二异氰酸酯(TDI)暴露可引起哮喘等肺部疾病。抑制高迁移率族蛋白B1(HMGB1)可减轻TDI对人支气管上皮(HBE)细胞的毒性作用。
方法：在这里，我们评估了HMGB1在TDI引起的哮喘小鼠中的体内积极作用，并探索了其在HBE细胞中的潜在机制。
结果：我们发现HMGB1的抑制明显减轻了哮喘小鼠肺组织的气道炎症、气道高反应性和气道重塑。体外实验结果表明，抑制HMGB1可改善TDI诱导的HBE细胞活性氧(ROS)释放、炎症反应和自噬激活。在分子水平上，抑制HMGB1可降低HMGB1、toll样受体4、波形蛋白和基质金属蛋白酶-9蛋白的表达，激活NF-κB和NOD样受体蛋白3 (NLRP3)炎症小体，增加E-钙黏蛋白的表达。重要的是，在TDI诱导的哮喘中，自噬的激活可能导致NLRP3炎症小体的过度激活。
结论;抑制HMGB1可通过ROS/AMPK/自噬途径减轻TDI诱导的哮喘，这可能为TDI诱导的哮喘的发病机制和治疗靶点提供有价值的证据。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Ecotoxicology and Environmental Safety 266 (2023) 115575 DOI: org/10.1016/j.ecoenv.2023.115575）
（Ecotoxicology and Environmental Safety 266 (2023) 115575 DOI: org/10.1016/j.ecoenv.2023.115575）
Inhibition of HMGB1 alleviates TDI-induced occupational asthma via the ROS/ AMPK/ autophagy pathway
Xiangjing Meng, Sumei Guo, Xiaoxia Zhang et al.
Abstract
BACKGROUND:Exposure to toluene diisocyanate (TDI) can cause pulmonary diseases such as asthma. Inhibition of high mobility group box 1 protein (HMGB1) has been found to be protective against the toxic effects of TDI on human bronchial epithelial (HBE) cells.
METHODS: Here, we evaluated the in vivo positive roles of HMGB1 in the TDI-caused asthma mice and explored its underlying mechanisms in HBE cells.
RESULTS:We found that suppression of HMGB1 obviously alleviated airway inflammation, airway hyperresponsiveness, and airway remodeling in the lung tissue of the asthma mice. The in vitro results showed that inhibition of HMGB1 ameliorated TDI-induced reactive oxygen species (ROS) release, inflammatory response, and activation of autophagy in HBE cells. At the molecular level, inhibition of HMGB1 decreased the expressions of HMGB1, Toll-like receptor 4, Vimentin and matrix metalloproteinase-9 proteins, activated NF-κB and NOD-like receptor protein 3 (NLRP3) inflammasome, and increased E-cadherin expression. Importantly, activation of autophagy could lead to the overactivation of NLRP3 inflammasome in TDI-induced asthma.
CONCLUSIONS: These results suggest that inhibition of HMGB1 can alleviate TDI-induced asthma through ROS/AMPK/autophagy pathways, which may provide valuable evidence for the pathogenesis and therapeutic targets of TDI-induced asthma.
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RNA结合蛋白ZFP36L1和ZFP36L2在人类和哮喘小鼠模型的气道上皮中表达失调
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线粒体生物标志物、城市居民暴露与6个月以上儿童哮喘结局的关联
