Genetic ablation of PARP-1 protects against oxazolone-induced contact hypersensitivity by modulating oxidative stress
Contact hypersensitivity (CHS) reaction is a form of delayed-type of hypersensitivity caused by contact allergens such as oxazolone (OXA). In previous studies it has been shown that poly(ADP-ribose) polymerase (PARP) inhibition reduces the extent of inflammation in CHS. We aimed to shed light on the molecular events causing the protective effect of PARP inhibitors. PARP-1 and -2 knockout mice were sensitized by abdominal delivery of OXA, and a week later CHS was induced by applying OXA on the ears of the mice. PARP-1(-/-) mice were protected against OXA-induced CHS in contrast to PARP-2(-/-) mice. In PARP-1(-/-) mice, neutrophil infiltration was reduced in line with the suppressed expression of proinflammatory cytokines, cell adhesion factors, and matrix metalloproteinase-9, which is likely because of impaired activation of NF-κB p65 and activating transcription factor-2, the two redox-sensitive transcription factors. Moreover, reduced nitrosative and oxidative stress was observed under inflammatory conditions in the PARP-1(-/-) mice when compared with PARP-1(+/+). In conclusion, PARP-1 activation is necessary for proinflammatory gene expression through which PARP-1 enhances neutrophil infiltration and hence oxidative/nitrosative stress, forming a vicious circle, and further aggravating the inflammatory process. Our data identify PARP-1 as a possible target in CHS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:130 |
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| Enthalten in: |
The Journal of investigative dermatology - 130(2010), 11 vom: 22. Nov., Seite 2629-37 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Brunyánszki, Attila [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.11.2010 Date Revised 25.11.2016 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/jid.2010.190 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM199418705 |
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| 100 | 1 | |a Brunyánszki, Attila |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Genetic ablation of PARP-1 protects against oxazolone-induced contact hypersensitivity by modulating oxidative stress |
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| 500 | |a Date Revised 25.11.2016 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Contact hypersensitivity (CHS) reaction is a form of delayed-type of hypersensitivity caused by contact allergens such as oxazolone (OXA). In previous studies it has been shown that poly(ADP-ribose) polymerase (PARP) inhibition reduces the extent of inflammation in CHS. We aimed to shed light on the molecular events causing the protective effect of PARP inhibitors. PARP-1 and -2 knockout mice were sensitized by abdominal delivery of OXA, and a week later CHS was induced by applying OXA on the ears of the mice. PARP-1(-/-) mice were protected against OXA-induced CHS in contrast to PARP-2(-/-) mice. In PARP-1(-/-) mice, neutrophil infiltration was reduced in line with the suppressed expression of proinflammatory cytokines, cell adhesion factors, and matrix metalloproteinase-9, which is likely because of impaired activation of NF-κB p65 and activating transcription factor-2, the two redox-sensitive transcription factors. Moreover, reduced nitrosative and oxidative stress was observed under inflammatory conditions in the PARP-1(-/-) mice when compared with PARP-1(+/+). In conclusion, PARP-1 activation is necessary for proinflammatory gene expression through which PARP-1 enhances neutrophil infiltration and hence oxidative/nitrosative stress, forming a vicious circle, and further aggravating the inflammatory process. Our data identify PARP-1 as a possible target in CHS | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Adjuvants, Immunologic |2 NLM | |
| 650 | 7 | |a Irritants |2 NLM | |
| 650 | 7 | |a Reactive Nitrogen Species |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
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| 700 | 1 | |a Hegedus, Csaba |e verfasserin |4 aut | |
| 700 | 1 | |a Szántó, Magdolna |e verfasserin |4 aut | |
| 700 | 1 | |a Erdélyi, Katalin |e verfasserin |4 aut | |
| 700 | 1 | |a Kovács, Katalin |e verfasserin |4 aut | |
| 700 | 1 | |a Schreiber, Valérie |e verfasserin |4 aut | |
| 700 | 1 | |a Gergely, Szabolcs |e verfasserin |4 aut | |
| 700 | 1 | |a Kiss, Borbála |e verfasserin |4 aut | |
| 700 | 1 | |a Szabó, Eva |e verfasserin |4 aut | |
| 700 | 1 | |a Virág, László |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Péter |e verfasserin |4 aut | |
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