Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII

Abstract

Environmental contextIncreasing commercial use of antimony is raising its environmental presence and thus possible effects on humans and ecosystems. An important uncertainty is the risk that exposure poses for biological systems. The present work explores the similarity in response of human epidermal keratinocytes, a known target cell type, to antimony and arsenic, where deleterious consequences of exposure to the latter are better known. AbstractSbIII and AsIII are known to exhibit similar chemical properties, but the degree of similarity in their effects on biological systems merits further exploration. The present work compares the responses of human epidermal keratinocytes, a known target cell type for arsenite-induced carcinogenicity, to these metalloids after treatment for 1 week at environmentally relevant concentrations. Previous work with these cells has shown that arsenite and antimonite have parallel effects in suppressing differentiation, altering levels of several critical enzymes and maintaining colony-forming ability. More globally, protein profiling now reveals parallels in SbIII and AsIII effects. The more sensitive technique of transcriptional profiling also shows considerable parallels. Thus, gene expression changes were almost entirely in the same directions for the two treatments, although the degree of change was sometimes significantly different. Inspection of the changes revealed that RYR1 and LRIG1 were among the genes strongly suppressed, consistent with reduced calcium-dependent differentiation and maintenance of epidermal growth factor-dependent proliferative potential. Moreover, levels of microRNAs in the cells were altered in parallel, with nearly 90% of the 198 most highly expressed ones being suppressed. Among these was miR-203, which is known to decrease proliferative potential. Finally, both SbIII and AsIII were seen to attenuate bone morphogenetic protein 6 induction of dual-specificity phosphatases 2 and 14, consistent with maintaining epidermal growth factor receptor signalling. These findings raise the question of whether SbIII, like AsIII, could act as a human skin carcinogen.