Poly(ADP-ribose) polymerase-1 depletion enhances the severity of inflammation in an imiquimod-induced model of psoriasis - PubMed (original) (raw)

doi: 10.1111/exd.14061. Epub 2019 Dec 6.

Affiliations

PMID: 31755591
DOI: 10.1111/exd.14061

Poly(ADP-ribose) polymerase-1 depletion enhances the severity of inflammation in an imiquimod-induced model of psoriasis

Borbála Kiss et al. Exp Dermatol. 2020 Jan.

Abstract

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.

Keywords: ARTD1; PARP1; imiquimod; keratinocyte differentiation; psoriasis.

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Poly(ADP-ribose) polymerase-1 depletion enhances the severity of inflammation in an imiquimod-induced model of psoriasis - PubMed (original) (raw)