Transcriptomic analysis of primary human keratinocytes ex-posed to cadmium chloride

Growing number of studies are aimed to investigate the impact of cadmium on human health. Cadmium-induced dermatotoxicity is an important field of research, but very numerous studies are focused on cadmium effect on human skin. Moreover, the vast studies were performed using HaCaT, but not primary keratinocytes. In this paper we provide the results describing the cytotoxic effect of cadmium exposure on primary human epidermal keratinocytes, obtained from different donors. The subtoxic concentration of cadmium chloride was determined via the MTT-assay, whereafter the transcriptomic analysis of the cells exposed to this concentration was performed. As in HaCaT cells, cadmium exposure results in the increased ROS level, cell cycle arrest and induction of apoptosis. Apart of that, we report that exposition with cadmium affects zinc and copper homeostasis, induces metallothionein expression and activates various signaling pathways, including Nrf2, NF-kB, TRAIL, PI3K. Cadmium induces secretion of various cytokines (IL-1, IL-6, IL-10, PGE2) and upregulates the expression of several cytokeratins, such as KRT6B, KRT6C, KRT16, KRT17. The obtained results enable a better understanding the mechanisms of cadmium-induced cytotoxicity and its effect on human epidermal skin cells.