Poly(ADP) ribose polymerase-1 ablation alters eicosanoid and docosanoid signaling and metabolism in a murine model of contact hypersensitivity

Borbála Kiss, Magdolna Szántó, Mónika Szklenár, Attila Brunyánszki, Tamás Marosvölgyi, Eszter Sárosi, Éva Remenyik, Pál Gergely, László Virág, Tamás Decsi, Ralph Rühl, Peter Bai

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11 Citations (Scopus)


Poly(ADP-ribose) polymerase (PARP)-1 is a pro-inflammatory protein. The inhibition of PARP-1 reduces the activity of numerous pro-inflammatory transcription factors, which results in the reduced production of pro-inflam-matory cytokines, chemokines, matrix metalloproteinases and inducible nitric oxide synthase, culminating in reduced inflam-mation of the skin and other organs. The aim of the present study was to investigate the effects of the deletion of PARP-1 expression on polyunsaturated fatty acids (PUFA), and PUFA metabolite composition, in mice under control conditions or undergoing an oxazolone (OXA)-induced contact hypersensitivity reaction (CHS). CHS was elicited using OXA in both the PARP-1+/+ and PARP-1-/- mice, and the concentration of PUFAs and PUFA metabolites in the diseased skin were assessed using lipidomics experiments. The levels of docosa-hexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were shown to be increased in the PARP-1-/- mice, as compared with the control, unsensitized PARP-1+/+ mice. In addition, higher expression levels of fatty acid binding protein 7 (FABP7) were detected in the PARP-1-/- mice. FABP7 is considered to be a specific carrier of DHA and EPA. Furthermore, the levels of the metabolites of DHA and EPA (considered mainly as anti-inflammatory or pro-resolving factors) were higher, as compared with the metabolites of arachidonic acid (considered mainly pro-inflammatory), both in the unsensitized control and OXA-sensitized PARP-1-/- mice. The results of the present study suggest that the genetic deletion of PARP-1 may affect the PUFA-homeostasis of the skin, resulting in an anti-inflammatory milieu, including increased DHA and EPA levels, and DHA and EPA metabolite levels. This may be an important component of the anti-inflammatory action of PARP-1 inhibition.

Original languageEnglish
Pages (from-to)2861-2867
Number of pages7
JournalMolecular Medicine Reports
Issue number4
Publication statusPublished - Apr 1 2015


  • Contact hypersensitivity
  • Cyclooxygenase-2
  • DHA
  • EPA
  • FABP7
  • Inflammation
  • Lipidomics
  • Oxazolone
  • PARP-1
  • PUFA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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