The Role of Protein Kinase C Isoforms in the Formation of Neutrophil Extracellular Traps

Q3 Agricultural and Biological Sciences Moscow University Biological Sciences Bulletin Pub Date : 2022-09-06 DOI:10.3103/s0096392522020122

N. V. Vorobjeva, S. S. Vakhlyarskaya, B. V. Chernyak

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引用次数: 1

Abstract

Neutrophils release decondensed nuclear chromatin or neutrophil extracellular traps (NET) in response to a great number of physiological and pharmacological stimuli. However, apart from the host defensive function, NETs play an essential role in the pathogenesis of various autoimmune, inflammatory, and malignant diseases. Therefore, understanding the molecular mechanisms of NET formation, usually leading to the neutrophil death (NETosis), is important to control the consequences of aberrant or excessive NET release. Protein kinase C (PKC) is a serine/threonine kinase that is involved in a variety of neutrophil functions, but its role in NETosis is not well understood. Since five PKC isoforms (α, βI, βII, δ, and ζ) have been described in human neutrophils, we studied their contribution to NETosis and oxidative burst using inhibitory analysis. Using specific PKC isoform inhibitors, we have shown that PKCβ, PKCδ, and PKCζ are involved in the oxidative burst and NETosis activated by calcium ionophore A23187, while PKCβ is involved in the oxidative burst and NETosis upon cell activation by diacylglycerol mimetic phorbol 12‑myristate 13-acetate.

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蛋白激酶C异构体在中性粒细胞胞外陷阱形成中的作用

摘要中性粒细胞释放去浓缩核染色质或中性粒细胞胞外陷阱(NET)，以响应大量的生理和药理刺激。然而，除了宿主防御功能外，NETs在各种自身免疫、炎症和恶性疾病的发病机制中起着重要作用。因此，了解通常导致中性粒细胞死亡(NETosis)的NET形成的分子机制，对于控制NET异常或过量释放的后果非常重要。蛋白激酶C (PKC)是一种丝氨酸/苏氨酸激酶，参与多种中性粒细胞功能，但其在NETosis中的作用尚不清楚。由于在人类中性粒细胞中描述了五种PKC亚型(α， βI， βII， δ和ζ)，我们使用抑制分析研究了它们对NETosis和氧化爆发的贡献。使用特异性PKC异构体抑制剂，我们发现PKCβ、PKCδ和PKCζ参与了钙离子载体A23187激活的氧化破裂和NETosis，而PKCβ参与了二酰基甘油模拟酚12 -肉豆肉酸13-醋酸酯激活的细胞氧化破裂和NETosis。

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来源期刊

Moscow University Biological Sciences Bulletin Agricultural and Biological Sciences-Agricultural and Biological Sciences (all)

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1.00

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期刊介绍： Moscow University Biological Sciences Bulletin is forum for research in all important areas of modern biology. It publishes original work on qualitative, analytical and experimental aspects of research. The scope of articles to be considered includes plant biology, zoology, ecology, evolutionary biology, biophysics, genetics, genomics, proteomics, molecular biology, cell biology, biochemistry, endocrinology, immunology, physiology, pharmacology, neuroscience, gerontology, developmental biology, bioinformatics, bioengineering, virology, and microbiology.