Buommino Elisabetta, Baroni Adone, Papulino Chiara, Nocera Francesca Paola, Coretti Lorena, Donnarumma Giovanna, De Filippis Anna, De Martino Luisa
Department of Pharmacy, University of Naples "Federico II,".
Department of Mental Health and Preventive Medicine, Dermatology Unit, University of Campania "Luigi Vanvitelli," Naples, Italy.
Med Mycol. 2018 Nov 1;56(8):987-993. doi: 10.1093/mmy/myy004.
Cytochrome P450 CYP1A1 and CYP1B1 enzymes are regulated by the aryl hydrocarbon receptor (AhR), a transcription factor activated by a variety of ligands among which Malassezia metabolites. In this study, we analyzed the modulation of CYP1A1, CYP1B1, and AhR in human keratinocytes infected with different strains of Malassezia pachydermatis, as well as the upregulation of some genes involved in the epidermal homeostasis. We demonstrated that all the strains induced AhR activation and its nuclear translocation in HaCaT cells infected for 24 h, compared to untreated cells. The expression of CYP1A1 and CYP1B1, prototypical markers of the AhR signaling pathway, were upregulated with the level of CYP1A1 mRNA approximately 100-fold greater than that for CYP1B1. Filaggrin, involucrin, and TGaseI, proteins involved in epidermal differentiation, were all modulated by Malassezia pachydermatis strains, with the strongest induction observed for filaggrin. By contrast, quinone oxidoreductase 1 (NQO1), which is part of the antioxidant defense system involved in detoxification, was not modulated in our experimental model. In conclusions, our findings suggest that Malassezia pachydermatis infection of human keratinocytes induces activation of the AhR, and increases the expression of its responsive genes and markers of epidermal differentiation, paving the way for occurrence/exacerbation of pathological skin conditions.
细胞色素P450 CYP1A1和CYP1B1酶受芳烃受体（AhR）调控，AhR是一种转录因子，可被多种配体激活，其中包括马拉色菌代谢产物。在本研究中，我们分析了感染不同厚皮马拉色菌菌株的人角质形成细胞中CYP1A1、CYP1B1和AhR的调节情况，以及一些参与表皮稳态的基因的上调情况。我们证明，与未处理的细胞相比，所有菌株在感染24小时的HaCaT细胞中均诱导了AhR激活及其核转位。AhR信号通路的典型标志物CYP1A1和CYP1B1的表达上调，CYP1A1 mRNA水平比CYP1B1大约高100倍。参与表皮分化的蛋白质丝聚合蛋白、兜甲蛋白和转谷氨酰胺酶I均受到厚皮马拉色菌菌株的调节，其中丝聚合蛋白的诱导作用最强。相比之下，参与解毒的抗氧化防御系统的一部分醌氧化还原酶1（NQO1）在我们的实验模型中未受到调节。总之，我们的研究结果表明，人角质形成细胞感染厚皮马拉色菌会诱导AhR激活，并增加其反应性基因的表达和表皮分化标志物，为病理性皮肤状况的发生/加重铺平了道路。
