PMN 中的 C/EBPε 及其乙酰化可增强对创伤的耐受性。

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Shaowen Cheng, Junyu Zhu, Yangyang Bian, Jiangling Yao, Wei Zhang, Shuangqin Yin, Tianyin Kuang, Lina Xian, Huaping Liang
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引用次数: 0

摘要

严重创伤可导致多种严重并发症,威胁患者的健康和生命。PMNs 的数量和功能在严重创伤时会发生迅速变化,在创伤反应中起着关键作用。CCAAT/增强子结合蛋白ε(C/EBPε)的缺失会严重损害多形核中性粒细胞(PMNs)的功能,而这一功能在创伤中至关重要。在本研究中,我们通过产生 C/EBPε 被敲除或过表达的小鼠,证实了 C/EBPε 可确保 PMN 功能的恢复,增强抗微生物蛋白的表达,从而促进创伤的恢复。此外,在创伤患者中观察到 C/EBPε 的表达减少,其水平与 ISS 和 APACHE II 评分呈负相关,这表明它有可能成为临床治疗的预后指标。从机理上讲,我们发现 SIRT1 的上调和 P300 的抑制参与了对 C/EBPε 乙酰化的抑制,从而降低了小鼠对创伤的恢复能力。作为治疗干预措施,无论是单独给予 PMN、NAM 治疗,还是两者结合使用,都能提高创伤小鼠的存活率。总之,我们的研究阐明了C/EBPε在增强创伤恢复能力中的作用,并确定了C/EBPε乙酰化是一种关键的调节机制,为涉及PMN输注和NAM治疗的潜在治疗方法提供了可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
C/EBPε and its acetylation in PMN enhance the tolerance to trauma.

Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of PMNs undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of polymorphonuclear neutrophils (PMNs), a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. As therapeutic interventions, whether through the sole administration of PMN, NAM treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment.

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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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