PDF(Pubmed)
Abstract：
Hyperinflammation characterized by elevated proinflammatory cytokines known as \'cytokine storms\' is the major cause of high severity and mortality seen in COVID-19 patients. The pathology behind the cytokine storms is currently unknown. Increased HMGB1 levels in serum/plasma of COVID-19 patients were reported by many studies, which positively correlated with the level of proinflammatory cytokines. Dead cells following SARS-CoV-2 infection might release a large amount of HMGB1 and RNA of SARS-CoV-2 into extracellular space. HMGB1 is a well-known inflammatory mediator. Additionally, extracellular HMGB1 might interact with SARS-CoV-2 RNA because of its high capability to bind with a wide variety of molecules including nucleic acids and could trigger massive proinflammatory immune responses. This review aimed to critically explore the many possible pathways by which HMGB1-SARS-CoV-2 RNA complexes mediate proinflammatory responses in COVID-19. The contribution of these pathways to impair host immune responses against SARS-CoV-2 infection leading to a cytokine storm was also evaluated. Moreover, since blocking the HMGB1-SARS-CoV-2 RNA interaction might have therapeutic value, some of the HMGB1 antagonists have been reviewed. The HMGB1- SARS-CoV-2 RNA complexes might trigger endocytosis via RAGE which is linked to lysosomal rupture, PRRs activation, and pyroptotic death. High levels of the proinflammatory cytokines produced might suppress many immune cells leading to uncontrolled viral infection and cell damage with more HMGB1 released. Altogether these mechanisms might initiate a proinflammatory cycle leading to a cytokine storm. HMGB1 antagonists could be considered to give benefit in alleviating cytokine storms and serve as a potential candidate for COVID-19 therapy.
摘要：
以被称为“细胞因子风暴”的促炎细胞因子升高为特征的过度炎症是COVID-19患者高严重程度和死亡率的主要原因。细胞因子风暴背后的病理学目前尚不清楚。许多研究报道了COVID-19患者血清/血浆中HMGB1水平升高，与促炎细胞因子水平呈正相关。SARS-CoV-2感染后的死细胞可能会释放大量的HMGB1和SARS-CoV-2的RNA进入细胞外空间。HMGB1是众所周知的炎症介质。此外,细胞外HMGB1可能与SARS-CoV-2RNA相互作用,因为它具有与包括核酸在内的多种分子结合的高能力,并可引发大量促炎免疫反应.这篇综述旨在批判性地探索HMGB1-SARS-CoV-2RNA复合物介导COVID-19促炎反应的许多可能途径。还评估了这些途径对削弱宿主针对SARS-CoV-2感染的免疫反应导致细胞因子风暴的贡献。此外，由于阻断HMGB1-SARS-CoV-2RNA相互作用可能具有治疗价值，已经综述了一些HMGB1拮抗剂。HMGB1-SARS-CoV-2RNA复合物可能通过与溶酶体破裂有关的RAGE触发内吞作用，PRRs激活和焦转性死亡。产生的高水平的促炎细胞因子可能抑制许多免疫细胞，导致不受控制的病毒感染和细胞损伤，释放更多的HMGB1。总之，这些机制可能会引发导致细胞因子风暴的促炎周期。HMGB1拮抗剂可被认为在缓解细胞因子风暴方面有益，并可作为COVID-19治疗的潜在候选者。本文受版权保护。保留所有权利。
