Pub Date : 2024-07-27DOI: 10.1134/s1022795424700406
A. K. Gribkova, A. E. Bigildeev, A. K. Shaytan
Abstract
Viral infections, including SARS-CoV-2, are accompanied by signs of systemic inflammation, which can cause long-term sequela for the patient. Time-stable changes in the organism may be caused by epigenetic shifts inherited in a series of cell divisions, in particular, by changes in the DNA methylation profile in cells of various organs and tissues in response to proinflammatory cytokines. IL1B is a key inflammatory factor, and it was shown that CpG methylation level in its promoter can change upon pro-inflammatory stimuli, and that it was associated with significant increase in IL1B expression. In particular, a specific CpG site in the promoter of the IL1B gene located 299 bp upstream from the transcription start site (CpG3) was previously shown to be an important player in these processes. In this study, we examined methylation/demethylation levels of this CpG3 in publicly available genome-wide methylation studies. A total of 15 dataset were analyzed that comprised data from stromal cells in normal and inflammation-associated states, immune cells of healthy young and aging donors, patients during COVID-19 and after recovery. The level of CpG3 demethylation was found to be higher in osteoarthritis samples of cartilage as compared to healthy donors in one dataset. In blood samples of patients with rheumatoid arthritis CpG3 demethylation was also found to be statistically higher than in healthy donors. In COVID-19 studies, blood samples obtained from patients with severe symptoms had higher CpG3 demethylation levels compared to samples obtained from patients with mild symptoms and controls. The level of CpG3 demethylation increased with age in healthy people as judged by whole blood samples. The same dependency was seen for in vitro cultures of mesenchymal cells obtained from healthy donors. Taken together we showed that demethylation level of a single CpG site in IL1B promoter increases in several cell types due to conditions associated with local and systemic inflammation, including SARS-CoV-2 infection, and in aging. These data suggest a possibility that a history of conditions associated with inflammation within an organism may be recorded, preserved, and encoded in its DNA methylation pattern. While the specificity of these “records of inflammation” is an open question, decoding the history of pathological events associated with inflammation that had been faced by the organism is an intriguing possibility.
{"title":"The Methylation Level of a CpG Site in the Human Interleukin-1β Promoter Reflects Both Current and Past Inflammation","authors":"A. K. Gribkova, A. E. Bigildeev, A. K. Shaytan","doi":"10.1134/s1022795424700406","DOIUrl":"https://doi.org/10.1134/s1022795424700406","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Abstract</h3><p>Viral infections, including SARS-CoV-2, are accompanied by signs of systemic inflammation, which can cause long-term sequela for the patient. Time-stable changes in the organism may be caused by epigenetic shifts inherited in a series of cell divisions, in particular, by changes in the DNA methylation profile in cells of various organs and tissues in response to proinflammatory cytokines. IL1B is a key inflammatory factor, and it was shown that CpG methylation level in its promoter can change upon pro-inflammatory stimuli, and that it was associated with significant increase in IL1B expression. In particular, a specific CpG site in the promoter of the <i>IL1B</i> gene located 299 bp upstream from the transcription start site (CpG3) was previously shown to be an important player in these processes. In this study, we examined methylation/demethylation levels of this CpG3 in publicly available genome-wide methylation studies. A total of 15 dataset were analyzed that comprised data from stromal cells in normal and inflammation-associated states, immune cells of healthy young and aging donors, patients during COVID-19 and after recovery. The level of CpG3 demethylation was found to be higher in osteoarthritis samples of cartilage as compared to healthy donors in one dataset. In blood samples of patients with rheumatoid arthritis CpG3 demethylation was also found to be statistically higher than in healthy donors. In COVID-19 studies, blood samples obtained from patients with severe symptoms had higher CpG3 demethylation levels compared to samples obtained from patients with mild symptoms and controls. The level of CpG3 demethylation increased with age in healthy people as judged by whole blood samples. The same dependency was seen for in vitro cultures of mesenchymal cells obtained from healthy donors. Taken together we showed that demethylation level of a single CpG site in <i>IL1B</i> promoter increases in several cell types due to conditions associated with local and systemic inflammation, including SARS-CoV-2 infection, and in aging. These data suggest a possibility that a history of conditions associated with inflammation within an organism may be recorded, preserved, and encoded in its DNA methylation pattern. While the specificity of these “records of inflammation” is an open question, decoding the history of pathological events associated with inflammation that had been faced by the organism is an intriguing possibility.</p>","PeriodicalId":21441,"journal":{"name":"Russian Journal of Genetics","volume":"55 1","pages":""},"PeriodicalIF":0.6,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141773861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}