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

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.

• Authors: Attila Brunyánszki, Csaba Hegedus, Magdolna Szántó, Katalin Erdélyi, Katalin Kovács, Valérie Schreiber, Szabolcs Gergely, Borbála Kiss, Eva Szabó, László Virág, Péter Bai
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 130 Issue 11 Pg. 2629-37 (Nov 2010) ISSN: 1523-1747 [Electronic] United States
• PMID: 20613774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Irritants
• Reactive Nitrogen Species
• Reactive Oxygen Species
• Oxazolone
• Parp1 protein, mouse
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases
• Parp2 protein, mouse

Topics

• Adjuvants, Immunologic (toxicity)
• Animals
• Cell Movement (immunology)
• Dermatitis, Contact (genetics, immunology, metabolism)
• Female
• Gene Deletion
• Irritants (toxicity)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutrophil Activation (physiology)
• Oxazolone (toxicity)
• Oxidative Stress (genetics)
• Poly (ADP-Ribose) Polymerase-1
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Reactive Nitrogen Species (metabolism)
• Reactive Oxygen Species (metabolism)