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Poly(ADP‐ribose) polymerase‐1 (PARP1) is a pro‐inflammatory protein, whose pro‐inflammatory properties were demonstrated in human. The pro‐inflammatory properties of PARP1 were shown in Th1‐ and Th2‐mediated inflammatory pathologies, but not Th17‐mediated inflammation. Thus, we studied the role of PARP1 in the imiquimod‐induced model of psoriasis. To our surprise, in imiquimod‐induced psoriasis, PARP1 acted as an anti‐inflammatory factor and its genetic deletion exacerbated symptoms. We showed that in the absence of PARP1, the epidermis thickened and the number of TUNEL‐positive cells decreased in the epidermis. These data indicate programmed cell death is decreased in keratinocytes. Changes in involucrin expression suggest that keratinocyte differentiation is hampered. Furthermore, epidermal expression of IL6 increased in the psoriasiform lesions of PARP1 knockout mice, suggesting that the inflammatory response is also derailed in the absence of PARP1. Finally, we showed that PARP1 expression is reduced in human psoriatic lesions compared with control skin samples. In imiquimod‐treated HPV‐KER keratinocytes, PARP inhibition recapitulated the in vivo findings, namely keratinocyte hyperproliferation; furthermore, the mRNA expression of psoriasis‐associated cytokines (IL6, IL1β, IL8, IL17 and IL23A) was also induced. The inhibition of TRPV1 abrogated the effects of the combined imiquimod + PARP inhibitor treatment. [ABSTRACT FROM AUTHOR]

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-inflammatory 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 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+/+ a nd PARP-1-/- 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 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. [ABSTRACT FROM AUTHOR]

PARP2, that belongs to the family of ADP-ribosyl transferase enzymes (ART), is a discovery of the millennium, as it was identified in 1999. Although PARP2 was described initially as a DNA repair factor, it is now evident that PARP2 partakes in the regulation or execution of multiple biological processes as inflammation, carcinogenesis and cancer progression, metabolism or oxidative stress-related diseases. Hereby, we review the involvement of PARP2 in these processes with the aim of understanding which processes are specific for PARP2, but not for other members of the ART family. A better understanding of the specific functions of PARP2 in all of these biological processes is crucial for the development of new PARP-centred selective therapies.