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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Autores principales: M. A. Shnayder, V. S. Shirinsky, N. Yu. Kalinovskaya, I. V. Shirinsky
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Lenguaje:RU
Publicado: SPb RAACI 2019
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spelling 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 DOAJ
collection 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
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