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Infiltration is accompa- nied by strong oxidative stress due to the formation of superoxide, nitric oxide, peroxynitrite, and further reac- tive species (Rowe et al., 1997; Ross et al., 1998). The poly(ADP-ribose) polymerase (PARP) superfamily consists of 17 members (Ame et al., 2004). A sub- group of these enzymes can be acti- vated by DNA single-strand breaks and aberrant DNA forms (Ame et al., 1999; Schreiber et al., 2006). In tissues and cells, PARP-1 is responsible for most of the PARP activity due to its abundance and high catalytic activity. Activated PARP-1 uses NAD þ as a substrate and synthesizes the formation of poly(ADP- ribose) polymers covalently attached to different acceptor proteins. The pre- sence of poly(ADP-ribose) polymers may regulate the functions of the acceptor proteins (Schreiber et al., 2006). Inhibition of PARP activity or knocking out the PARP-1 gene has been shown to suppress inflammatory reactions such as colitis, arthritis, and uveitis (Shall and De Murcia, 2000; Virag and Szabo, 2002; Cuzzocrea, 2005). Prevention of cellular dysfunc- tion and inhibition of NF-kB activation have been proposed to be the mechan- isms underlying the anti-inflammatory effects of PARP inhibition/knockout (Virag and Szabo, 2002). Poly(ADP-ribose) polymerase plays a role in the regulation of the transcrip- tion of various inflammatory mediators such as cytokines, chemokines, induci- ble nitric oxide synthase, and matrix metalloproteinases (MMPs). In our previous report, we have demonstrated peroxynitrite production, DNA breakage, and poly(ADP-ribose) formation during the elicitation phase of the CHS (Szabo et al., 2001). More- over, we have shown that peroxynitrite, superoxide, and hydrogen peroxide impair proliferation and viability of HaCaT keratinocytes (Szabo et al., 2001). PARP inhibitors prevented necrotic cell death with a slight in- crease in apoptotic DNA fragmentation and also reduced cytokine-induced ex- pression of IL-8 and ICAM-1 in HaCaT cells. (Szabo et al., 2001). Kehe et al. (2008) reported similar findings in a model of sulfur mustard-induced cell death of HaCaT cells. They also found Abbreviations: CHS, contact hypersensitivity; MMP, matrix metalloproteinase; MPO, myeloperoxidase; PARP, poly(ADP-ribose) polymerase; ROI, reactive oxygen intermediate; RNI, reactive nitrogen intermediate; TIMP, tissue inhibitor of metalloproteinases 234 Journal of Investigative Dermatology (2009), Volume 129 P Bai et al. PARP Mediates CHS