THP1-based cybrid cells with various mtDNA mutations differ by the ability to form inflammatory response
- 作者: Zhuravlev A.1,2, Verkhova S.1,2, Kubekina M.3
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隶属关系:
- Institute of General Pathology and Pathophysiology
- Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
- Core Facility Center and Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences
- 期: 卷 27, 编号 2 (2024)
- 页面: 139-144
- 栏目: SHORT COMMUNICATIONS
- URL: https://journals.rcsi.science/1028-7221/article/view/263655
- DOI: https://doi.org/10.46235/1028-7221-16781-TCC
- ID: 263655
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Most age-related human diseases are accompanied by chronic inflammation. Modern research is aimed at studying the principles of the formation of the immune response. The reasons why the local inflammatory reaction cannot be resolved and becomes a sluggish chronic form are still unknown. Immune cells secrete cytokines in response to pathogens. To avoid cell death as a result of high concentrations of cytokines and resulting tissue damage, there is a mechanism of innate immune tolerance. Innate immune tolerance involves a decrease in the secretion of proinflammatory cytokines in response to repeated exposure to a pathogen. It is known that mitochondria play an important role in the formation of the immune response. Consequently, impaired mitochondrial function can lead to impaired immune response. To control the quality of mitochondria in the cell, there is a mechanism – mitophagy. Previously, we have created cybrid lines based on the monocytic cell line THP-1. Cybrids were obtained by fusion of THP-1 cells (mitochondria were removed) with platelets from patients. Each of the cybrid lines had the THP-1 nuclear genome and an individual patient’s mitochondrial genome. In our study, we decided to study the ability of cells carrying different mitochondrial genomes to generate a proinflammatory response, as well as to form tolerance in the future. For this purpose, we chose a model of ecdotoxin tolerance. Thus, we stimulated the cybrid lines twice with lipopolysaccharide and then assessed the secretion of the cytokines TNFα, IL-1β, IL-6, IL-8, and CCL2 using ELISA. The cybrids demonstrated two levels of proinflammatory response: high and low. Moreover, cybrids with a high proinflammatory response either did or did not develop tolerance upon repeated stimulation. In our study, cells that differed from each other only in mitochondrial genome demonstrated three types of reactions upon the induction of immune tolerance to LPS. Future studies will improve our understanding of the mechanisms of mitochondrial involvement in pathological processes. It is likely that studies of deficient mitophagy and the role of certain mtDNA mutations in its development will yield promising results.
作者简介
A. Zhuravlev
Institute of General Pathology and Pathophysiology; Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
编辑信件的主要联系方式.
Email: Zhuravel17@yandex.ru
Postgraduate Student, Junior Researcher Associate, Laboratory of Angiopathology; Junior Research Associate
俄罗斯联邦, Moscow; MoscowS. Verkhova
Institute of General Pathology and Pathophysiology; Avtsyn Research Institute of Human Morphology, Petrovsky National Research Centre of Surgery
Email: Zhuravel17@yandex.ru
Senior Assistant; Postgraduate Student
俄罗斯联邦, Moscow; MoscowM. Kubekina
Core Facility Center and Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences
Email: Zhuravel17@yandex.ru
PhD (Biology), Research Associate
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