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001-es BibID:	BIBFORM114252
035-os BibID:	(cikkazonosító)1186369 (scopus)85168475682 (wos)001052448900001
Első szerző:	Pan, Lang
Cím:	Substrate-specific binding of 8-oxoguanine DNA glycosylase 1 (OGG1) reprograms mucosal adaptations to chronic airway injury / Pan Lang, Vlahopoulos Spiros, Tanner Lloyd, Bergwik Jesper, Bacsi Attila, Radak Zsolt, Egesten Arne, Ba Xueqing, Brasier Allan R., Boldogh Istvan
Dátum:	2023
ISSN:	1664-3224
Megjegyzések:	Recent advances have uncovered the non-random distribution of 7, 8-dihydro-8-oxoguanine (8-oxoGua) induced by reactive oxygen species, which is believed to have epigenetic effects. Its cognate repair protein, 8-oxoguanine DNA glycosylase 1 (OGG1), reads oxidative substrates and participates in transcriptional initiation. When redox signaling is activated in small airway epithelial cells, the DNA repair function of OGG1 is repurposed to transmit acute inflammatory signals accompanied by cell state transitions and modification of the extracellular matrix. Epithelial-mesenchymal and epithelial-immune interactions act cooperatively to establish a local niche that instructs the mucosal immune landscape. If the transitional cell state governed by OGG1 remains responsive to inflammatory mediators instead of differentiation, the collateral damage provides positive feedback to inflammation, ascribing inflammatory remodeling to one of the drivers in chronic pathologies. In this review, we discuss the substrate-specific read through OGG1 has evolved in regulating the innate immune response, controlling adaptations of the airway to environmental and inflammatory injury, with a focus on the reader function of OGG1 in initiation and progression of epithelial to mesenchymal transitions in chronic pulmonary disease.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Frontiers in Immunology. - 14 (2023), p. 1-12. -
További szerzők:	Vlahopoulos, Spiros A. Tanner, Lloyd Bergwik, Jesper Bácsi Attila (1967-) (immunológus) Radák Zsolt Egesten, Arne Ba, Xueqing Brasier, Allan R. Boldogh István
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM114251
035-os BibID:	(scopus)85168388624 (wos)001050570800001 (cikkazonosító)1161160
Első szerző:	Xue, Yaoyao
Cím:	Epigenetic control of type III interferon expression by 8-oxoguanine and its reader 8-oxoguanine DNA glycosylase1 / Xue Yaoyao, Pan Lang, Vlahopoulos Spiros, Wang Ke, Zheng Xu, Radak Zsolt, Bacsi Attila, Tanner Lloyd, Brasier Allan R., Ba Xueqing, Boldogh Istvan
Dátum:	2023
ISSN:	1664-3224
Megjegyzések:	Interferons (IFNs) are secreted cytokines with the ability to activate expression of IFN stimulated genes that increase resistance of cells to virus infections. Activated transcription factors in conjunction with chromatin remodelers induce epigenetic changes that reprogram IFN responses. Unexpectedly, 8-oxoguanine DNA glycosylase1 (Ogg1) knockout mice show enhanced stimuli-driven IFN expression that confers increased resistance to viral and bacterial infections and allergen challenges. Here, we tested the hypothesis that the DNA repair protein OGG1 recognizes 8-oxoguanine (8-oxoGua) in promoters modulating IFN expression. We found that functional inhibition, genetic ablation, and inactivation by post-translational modification of OGG1 significantly augment IFN-? expression in epithelial cells infected by human respiratory syncytial virus (RSV). Mechanistically, OGG1 bound to 8-oxoGua in proximity to interferon response elements, which inhibits the IRF3/IRF7 and NF-?B/RelA DNA occupancy, while promoting the suppressor NF-?B1/p50-p50 homodimer binding to the IFN-?2/3 promoter. In a mouse model of bronchiolitis induced by RSV infection, functional ablation of OGG1 by a small molecule inhibitor (TH5487) enhances IFN-? production, decreases immunopathology, neutrophilia, and confers antiviral protection. These findings suggest that the ROS-generated epigenetic mark 8-oxoGua via its reader OGG1 serves as a homeostatic thresholding factor in IFN-? expression. Pharmaceutical targeting of OGG1 activity may have clinical utility in modulating antiviral response.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Frontiers in Immunology. - 14 (2023), p. 1-19. -
További szerzők:	Pan, Lang Vlahopoulos, Spiros A. Wang, Ke Zheng, Xu Radák Zsolt Bácsi Attila (1967-) (immunológus) Tanner, Lloyd Brasier, Allan R. Ba, Xueqing Boldogh István
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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