THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY
The effects DNA methylation modulators on pro- and anti-inflammatory cytokine production by fibroblast-like synoviocytes (FLS) were evaluated using FLS obtained from synovial tissues of 8 patients with active RA and cultivated for 3-7 passages in vitro. It was shown that fenofibrate did not change...
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2019
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oai:doaj.org-article:b84e3803eabe4ef3822a06086126ccaa2021-11-18T08:03:48ZTHE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY1563-06252313-741X10.15789/1563-0625-2019-2-231-238https://doaj.org/article/b84e3803eabe4ef3822a06086126ccaa2019-05-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1523https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThe effects DNA methylation modulators on pro- and anti-inflammatory cytokine production by fibroblast-like synoviocytes (FLS) were evaluated using FLS obtained from synovial tissues of 8 patients with active RA and cultivated for 3-7 passages in vitro. It was shown that fenofibrate did not change levels of 5-methylcytosine (5-MeC) in FLS, genistein and ademetionine increased 5-MeC concentrations by 35%, and hydralazine resulted in twofold decrease of 5-MeC levels.There was a spontaneous production of IL-6, IL-17, IL- 18, and IL-10 by FLS cultures, an addition of IL-1β to cultures resulted in significant up-regulation of these cytokines synthesis. DNA methylation donors decreased IL-6 production by FLS. In contrast with hydralazine and genistein, ademetionine decreased IL-6 production by FLS. Synthesis of IL-17 was down-regulated with the addition of DNA-methylation modulators in low doses while there was no effect on IL-10 production. In conclusion, the effects of DNA-methylation modulators on production of pro- and anti-inflammatory cytokines by FLS is not only due to their impact on DNA methylation, but may be linked to other epigenetic mechanisms. FSC cultures may be used as a tool for preclinical assessment of new DNA methylation modulators.M. A. ShnayderV. S. ShirinskyN. Yu. KalinovskayaI. V. ShirinskySPb RAACIarticlefibroblast-like synovial cellsrheumatoid arthritisdna methylationcytokinesgenisteinhydralazineademethionineImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 21, Iss 2, Pp 231-238 (2019) |
institution |
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DOAJ |
language |
RU |
topic |
fibroblast-like synovial cells rheumatoid arthritis dna methylation cytokines genistein hydralazine ademethionine Immunologic diseases. Allergy RC581-607 |
spellingShingle |
fibroblast-like synovial cells rheumatoid arthritis dna methylation cytokines genistein hydralazine ademethionine Immunologic diseases. Allergy RC581-607 M. A. Shnayder V. S. Shirinsky N. Yu. Kalinovskaya I. V. Shirinsky THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY |
description |
The effects DNA methylation modulators on pro- and anti-inflammatory cytokine production by fibroblast-like synoviocytes (FLS) were evaluated using FLS obtained from synovial tissues of 8 patients with active RA and cultivated for 3-7 passages in vitro. It was shown that fenofibrate did not change levels of 5-methylcytosine (5-MeC) in FLS, genistein and ademetionine increased 5-MeC concentrations by 35%, and hydralazine resulted in twofold decrease of 5-MeC levels.There was a spontaneous production of IL-6, IL-17, IL- 18, and IL-10 by FLS cultures, an addition of IL-1β to cultures resulted in significant up-regulation of these cytokines synthesis. DNA methylation donors decreased IL-6 production by FLS. In contrast with hydralazine and genistein, ademetionine decreased IL-6 production by FLS. Synthesis of IL-17 was down-regulated with the addition of DNA-methylation modulators in low doses while there was no effect on IL-10 production. In conclusion, the effects of DNA-methylation modulators on production of pro- and anti-inflammatory cytokines by FLS is not only due to their impact on DNA methylation, but may be linked to other epigenetic mechanisms. FSC cultures may be used as a tool for preclinical assessment of new DNA methylation modulators. |
format |
article |
author |
M. A. Shnayder V. S. Shirinsky N. Yu. Kalinovskaya I. V. Shirinsky |
author_facet |
M. A. Shnayder V. S. Shirinsky N. Yu. Kalinovskaya I. V. Shirinsky |
author_sort |
M. A. Shnayder |
title |
THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY |
title_short |
THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY |
title_full |
THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY |
title_fullStr |
THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY |
title_full_unstemmed |
THE PRODUCTION OF PRO- AND ANTIINFLAMMATORY CYTOKINES BY SYNOVIAL FIBROBLASTS OF PATIENTS WITH RHEUMATOID ARTHRITIS IN VITRO WHEN USING DNA METHYLATION MODULATORS - INVESTIGATIVE STUDY |
title_sort |
production of pro- and antiinflammatory cytokines by synovial fibroblasts of patients with rheumatoid arthritis in vitro when using dna methylation modulators - investigative study |
publisher |
SPb RAACI |
publishDate |
2019 |
url |
https://doaj.org/article/b84e3803eabe4ef3822a06086126ccaa |
work_keys_str_mv |
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