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

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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
Volume11
Issue number4
DOIs
Publication statusPublished - Apr 1 2015

Keywords

  • 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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