Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Exp Dermatol. 2020 Jan;29(1):79-85. doi: 10.1111/exd.14061. Epub 2019 Dec 6.
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.
聚（ADP-核糖）聚合酶 1（PARP1）是一种促炎蛋白，其促炎特性已在人类中得到证实。PARP1 的促炎特性在 Th1 和 Th2 介导的炎症性病理中得到了证明，但在 Th17 介导的炎症中没有。因此，我们研究了 PARP1 在咪喹莫特诱导的银屑病模型中的作用。令我们惊讶的是，在咪喹莫特诱导的银屑病中，PARP1 作为一种抗炎因子，其基因缺失加剧了症状。我们表明，在缺乏 PARP1 的情况下，表皮变厚，表皮中 TUNEL 阳性细胞的数量减少。这些数据表明角质形成细胞中的程序性细胞死亡减少。角蛋白表达的变化表明角质形成细胞分化受阻。此外，PARP1 基因敲除小鼠银屑病样病变中表皮白细胞介素 6（IL6）表达增加，表明在缺乏 PARP1 的情况下炎症反应也失调。最后，我们发现与对照皮肤样本相比，PARP1 在人银屑病病变中的表达减少。在咪喹莫特处理的 HPV-KER 角质形成细胞中，PARP 抑制再现了体内发现的结果，即角质形成细胞过度增殖；此外，银屑病相关细胞因子（IL6、IL1β、IL8、IL17 和 IL23A）的 mRNA 表达也被诱导。TRPV1 的抑制消除了咪喹莫特+PARP 抑制剂联合治疗的影响。
