Összesen 2 találat.


001-es BibID:BIBFORM080824
Első szerző:Pázmándi Kitti Linda (molekuláris biológus, immunológus)
Cím:Oxidized base 8-oxoguanine, a product of DNA repair processes, contributes to dendritic cell activation / Kitti Pázmándi, Máté Sütő, Tünde Fekete, Aliz Varga, Eszter Boldizsár, István Boldogh, Attila Bácsi
Megjegyzések:A growing body of evidence suggests that elevated levels of reactive oxygen species (ROS) in the airways caused by exposure to gas phase pollutants or particulate matter are able to activate dendritic cells (DCs); however, the exact mechanisms are still unclear. When present in excess, ROS can modify macromolecules including DNA. One of the most abundant DNA base lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which is repaired by the 8-oxoguanine DNA glycosylase 1 (OGG1)-initiated base excision repair (BER) (OGG1-BER) pathway. Studies have also demonstrated that in addition to its role in repairing oxidized purines, OGG1 has guanine nucleotide exchange factor activity when bound to 8-oxoG. In the present study, we tested the hypothesis that exposure to 8-oxoG, the specific product of OGG1-BER, induces functional changes of DCs. Supporting our hypothesis, transcriptome analysis revealed that in mouse lungs, out of 95 genes associated with DCs' function, 22 or 42 were significantly upregulated after a single or multiple intranasal 8-oxoG challenges, respectively. In a murine model of allergic airway inflammation, significantly increased serum levels of ovalbumin (OVA)-specific IgE antibodies were detected in mice sensitized via nasal challenges with OVA+8-oxoG compared to those challenged with OVA alone. Furthermore, exposure of primary human monocyte-derived DCs (moDC) to 8-oxoG base resulted in significantly enhanced expression of cell surface molecules (CD40, CD86, CD83, HLA-DQ) and augmented the secretion of pro-inflammatory mediators IL-6, TNF and IL-8, whereas it did not considerably influence the production of the anti-inflammatory cytokine IL-10. The stimulatory effects of 8-oxoG on human moDCs were abolished upon siRNA-mediated OGG1 depletion. Collectively, these data suggest that OGG1-BER-generated 8-oxoG base-driven cell signaling activates DCs, which may contribute to initiation of both the innate and adaptive immune responses under conditions of oxidative stress.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Free Radical Biology and Medicine. - 143 (2019), p. 209-220. -
További szerzők:Sütő Máté István (1991-) (molekuláris biológus) Fekete Tünde (1984-) (immunológus, molekuláris biológus, mikrobiológus) Varga Alíz (1983-) (immunológus) Boldizsár Eszter Boldogh István Bácsi Attila (1967-) (immunológus)
Pályázati támogatás:EFOP-3.6.3-VEKOP-16-2017-00009
NKFIH K 109595
NKFIH K 125337
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat


001-es BibID:BIBFORM055554
Első szerző:Pázmándi Kitti Linda (molekuláris biológus, immunológus)
Cím:Oxidative modification enhances the immunostimulatory effects of extracellular mitochondrial DNA on plasmacytoid dendritic cells / Kitti Pazmandi, Zsofia Agod, Brahma V. Kumar, Attila Szabo, Tunde Fekete, Viktoria Sogor, Agota Veres, Istvan Boldogh, Eva Rajnavolgyi, Arpad Lanyi, Attila Bacsi
Megjegyzések:Inflammation is associated with oxidative stress and characterized by elevated levels of damage-associated molecular pattern (DAMP) molecules released from injured or even living cells into the surrounding microenvironment. One of these endogenous danger signals is the extracellular mitochondrial DNA (mtDNA) containing evolutionary conserved unmethylated CpG repeats. Increased levels of reactive oxygen species (ROS) generated by recruited inflammatory cells modify mtDNA oxidatively resulting primarily in accumulation of 8-oxo-7,8-dihydroguanine (8-oxoG) lesions. In this study, we examined the impact of native and oxidatively modified mtDNAs on the phenotypic and functional properties of plasmacytoid dendritic cells (pDCs), which possess a fundamental role in the regulation of inflammation and T cell immunity. Treatment of human primary pDCs with native mtDNA up-regulated the expression of a co-stimulatory molecule (CD86), a specific maturation marker (CD83), and a main antigen-presenting molecule (HLA-DQ) on the cell surface, as well as increased TNF-? and IL-8 production from the cells. These effects were more apparent when pDCs were exposed to oxidatively modified mtDNA. Neither native nor oxidized mtDNA molecules were able to induce interferon (IFN)-? secretion from pDCs unless they formed a complex with human cathelicidin LL-37, an antimicrobial peptide. Interestingly, simultaneous administration of a Toll-like receptor (TLR)9 antagonist abrogated the effects of both native and oxidized mtDNAs on human pDCs. In a murine model, oxidized mtDNA also proved a more potent activator of pDCs compared to the native form, except for induction of IFN-? production. Collectively, we demonstrate here for the first time that elevated levels of 8-oxoG bases in the extracellular mtDNA induced by oxidative stress increase the immunostimulatory capacity of mtDNA on pDCs.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Plasmacytoid dendritic cells
Extracellular mitochondrial DNA
Oxidative stress
8-oxoguanine base
Megjelenés:Free Radical Biology and Medicine. - 77 (2014), p. 281-290. -
További szerzők:Agod Zsófia Kumar, Brahma V. Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Fekete Tünde (1984-) (immunológus, molekuláris biológus, mikrobiológus) Somogyi Viktória (1989-) (biotechnológus) Veres Ágota (laboráns) Boldogh István Rajnavölgyi Éva (1950-) (immunológus) Lányi Árpád (1962-) (biológus, immunológus) Bácsi Attila (1967-) (immunológus)
Pályázati támogatás:K-109595
Internet cím:Szerző által megadott URL
Intézményi repozitóriumban (DEA) tárolt változat
Rekordok letöltése1