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由中细胞释放的HMGB1驱动着由石棉诱导的中瘤的发展

Joelle S Suarez¹, Flavia Novelli¹, Keisuke Goto^1,2

¹Thoracic Oncology, University of Hawaii Cancer Center, Honolulu, HI 96813.

Proceedings of the National Academy of Sciences of the United States of America

|September 20, 2023

概括

高流动性组盒1 (HMGB1) 由中细胞释放的驱动石棉诱导的中瘤. 间皮质HMGB1淘汰小鼠显示炎症和间皮质瘤发病率降低,突出显示HMGB1是关键驱动因素.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
毒理学毒理学毒理学

背景情况:

接触石棉是恶性间皮瘤的主要原因.
高流动性组盒子1 (HMGB1) 释放与石棉诱导的间皮瘤病原发生有关.
细胞外HMGB1在间皮瘤发展中的细胞源仍然不清楚.

研究的目的:

确定中质细胞还是炎症细胞是石棉诱导中质瘤中HMGB1的主要来源.
研究介质细胞HMGB1在驱动炎症和介质细胞瘤发展中的作用.
确定潜在的治疗点,以预防或治疗由石棉诱导的间皮瘤.

主要方法:

开发条件介质细胞HMGB1-Knockout (Hmgb1ΔpMeso) 和骨髓单细胞系HMGB1-Knockout (Hmgb1ΔMylc) 的小鼠模型.
在淘汰赛小鼠中,分析炎症反应,细胞因子分泌 (TNFα) 和巨细胞两极分化在暴露于石棉后.
在开发的小鼠模型中评估间皮瘤发病率和生存率.

主要成果:

在暴露于石棉后的早期炎症期间,HMGB1主要由中细胞产生和释放.
介质细胞HMGB1淘汰赛小鼠表现出减少的炎症反应,降低TNFα分泌和改变的M1/M2巨细胞比率.
Hmgb1ΔpMeso小鼠表现出延迟和减少间皮瘤发病率,以及增加间皮瘤特异性存活率.

结论:

介质质细胞衍生的HMGB1是石棉诱导的介质质瘤的关键驱动因素.
向从中细胞释放的HMGB1可能提供一种新的预防或治疗策略.
这项研究阐明了HMGB1促进间皮瘤发展的生物机制.

关键词:

这就是HMGB1的特点.石棉是一种石棉.巨细胞是什么?巨细胞是什么?半质瘤 (Mesothelioma) 是一种中质瘤.微观环境是一个微观环境.

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