Genome-wide transcriptome induced by nickel in human monocytes.

摘要: Abstract Nickel-containing alloys are frequently used in the biomedical field, although, owing to corrosive processes metal ion leaching is inevitable. Due nickel (Ni2+) several adverse effects described literature. However, only a few studies evaluated genetic profile of Ni2+ human cells which great importance since nickel-induced differ between humans and mice as result species-specific receptor variability. Thus, we investigated gene expression induced by Ni2+in monocytes using transcriptome-wide approach determining new target genes implicated pathologies. Monocytes were isolated from healthy volunteers Central European origin stringent inclusion criteria. Cells challenged with different concentrations. Array-based analysis was performed comprising more than 47,000 transcripts followed pathway analyses. Transcriptional data validated protein cell surface markers. significantly influenced 1385 dose-dependent manner. Apart known targets (CCL20↑, PTGS2↑, MTs↑, SLCs↑), identified candidates Ni2+-elicited (various microRNAs↑, INSIG1↑, NAMPT↑, MS4A6A↓, DHRS9↓). Several these correspond immunity, inflammation shown be involved cellular reactions related hypersensitivity, cancer, colitis, encephalitis. Moreover, 459 canonical pathways/signaling, 500 pathologies 2687 upstream regulators detected. Protein results our findings. To knowledge, present systematic study first explored responses primary identifying genes, pathways relevance diagnostic therapeutic strategies. Statement Significance Nickel widely applied although documented literature due leaching. In humans, allergic like contact dermatitis most common effect Ni2+, whereas serious concerns relate possible systemic carcinogenic activities. Using genome-wide transcriptional unveil nickel-elicited immune response significance This provides information how host-derived contributes interaction antigens supports interplay ions diseases.