Journal
JOURNAL OF INVESTIGATIVE DERMATOLOGY
Volume 130, Issue 11, Pages 2629-2637Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/jid.2010.190
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Funding
- Bolyai
- SNSF
- FEBS
- OTKA [NNF78498, K73003, K60780, K82009, TAMOP-4.2.2-08/1-2008-0019]
- NKTH
- Mecenatura [DE OEC Mec-1/2008]
- Ambassade de France en Hongrie and Ministere des Affaires Etrangeres
- Hungarian Science and Technology Foundation [FR-26/2009]
- Association pour la Recherche sur le Cancer
- Centre National de la Recherche Scientifique
- Universite de Strasbourg
- Agence Nationale de la Recherche
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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-kappa B 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.
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