Genetic ablation of PARP-1 protects against oxazolone-induced contact hypersensitivity by modulating oxidative stress

Attila Brunyánszki, Csaba Hegedüs, Magdolna Szántó, Katalin Erdélyi, Katalin Kovács, Valérie Schreiber, Szabolcs Gergely, Borbála Kiss, Éva Szabó, László Virág, Péter Bai

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Abstract

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.

Original languageEnglish
Pages (from-to)2629-2637
Number of pages9
JournalJournal of Investigative Dermatology
Volume130
Issue number11
DOIs
Publication statusPublished - Nov 2010

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Brunyánszki, A., Hegedüs, C., Szántó, M., Erdélyi, K., Kovács, K., Schreiber, V., Gergely, S., Kiss, B., Szabó, É., Virág, L., & Bai, P. (2010). Genetic ablation of PARP-1 protects against oxazolone-induced contact hypersensitivity by modulating oxidative stress. Journal of Investigative Dermatology, 130(11), 2629-2637. https://doi.org/10.1038/jid.2010.190