Deregulated DNA damage response network in Behcet's disease
Copyright © 2022 Elsevier Inc. All rights reserved..
Behcet's disease (BD) is a chronic, relapsing systemic vasculitis of unknown etiology. Since the DNA repair enzyme NEIL1 has been identified as one of the two genetic risk factors for BD by whole exome study, we examined the potential involvement of the DNA damage response (DDR) network in BD. Peripheral blood mononuclear cells from 26 patients and 26 age-/sex-matched healthy controls were studied. Endogenous DNA damage levels were increased in active BD patients compared to controls or patients in remission. In parallel, BD patients had defective nucleotide excision repair capacity. RNA-sequencing revealed reduced expression of NEIL1 that negatively correlated with DNA damage accumulation. On the other hand, expression of genes involved in senescence and senescence-associated secretory phenotype positively correlated with individual endogenous DNA damage levels. We conclude that deregulated DDR contributes to the proinflammatory environment in BD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:246 |
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| Enthalten in: |
Clinical immunology (Orlando, Fla.) - 246(2023) vom: 20. Jan., Seite 109189 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vlachogiannis, Nikolaos I [VerfasserIn] |
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| Links: |
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| Themen: |
Behcet's disease |
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| Anmerkungen: |
Date Completed 17.01.2023 Date Revised 12.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.clim.2022.109189 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Behcet's disease (BD) is a chronic, relapsing systemic vasculitis of unknown etiology. Since the DNA repair enzyme NEIL1 has been identified as one of the two genetic risk factors for BD by whole exome study, we examined the potential involvement of the DNA damage response (DDR) network in BD. Peripheral blood mononuclear cells from 26 patients and 26 age-/sex-matched healthy controls were studied. Endogenous DNA damage levels were increased in active BD patients compared to controls or patients in remission. In parallel, BD patients had defective nucleotide excision repair capacity. RNA-sequencing revealed reduced expression of NEIL1 that negatively correlated with DNA damage accumulation. On the other hand, expression of genes involved in senescence and senescence-associated secretory phenotype positively correlated with individual endogenous DNA damage levels. We conclude that deregulated DDR contributes to the proinflammatory environment in BD | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Souliotis, Vassilis L |e verfasserin |4 aut | |
| 700 | 1 | |a Sfikakis, Petros P |e verfasserin |4 aut | |
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