Poly(ADP) ribose polymerase-1 ablation alters eicosanoid and docosanoid signaling and metabolism in a murine model of contact hypersensitivity.
Mol Med Rep
; 11(4): 2861-7, 2015 Apr.
Article
en En
| MEDLINE
| ID: mdl-25482287
ABSTRACT
Poly(ADPribose) polymerase (PARP)1 is a proinflammatory protein. The inhibition of PARP1 reduces the activity of numerous proinflammatory transcription factors, which results in the reduced production of proinflammatory cytokines, chemokines, matrix metalloproteinases and inducible nitric oxide synthase, culminating in reduced inflammation of the skin and other organs. The aim of the present study was to investigate the effects of the deletion of PARP1 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 PARP1+/+ and PARP1/ mice, and the concentration of PUFAs and PUFA metabolites in the diseased skin were assessed using lipidomics experiments. The levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were shown to be increased in the PARP1/ mice, as compared with the control, unsensitized PARP1+/+ mice. In addition, higher expression levels of fatty acid binding protein 7 (FABP7) were detected in the PARP1/ 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 antiinflammatory or proresolving factors) were higher, as compared with the metabolites of arachidonic acid (considered mainly proinflammatory), both in the unsensitized control and OXAsensitized PARP1/ mice. The results of the present study suggest that the genetic deletion of PARP1 may affect the PUFAhomeostasis of the skin, resulting in an antiinflammatory milieu, including increased DHA and EPA levels, and DHA and EPA metabolite levels. This may be an important component of the antiinflammatory action of PARP1 inhibition.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Eicosanoides
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Poli(ADP-Ribosa) Polimerasas
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Dermatitis por Contacto
Tipo de estudio:
Etiology_studies
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Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article