Genome-wide transcriptome induced by nickel in human monocytes

Area of Science:

• Biomedical Engineering
• Immunology
• Toxicology

Background:

• Nickel-containing alloys are common in biomedical applications, but nickel ion (Ni(2+)) leaching can cause adverse effects.
• Human responses to Ni(2+) differ from other species, necessitating studies in human cells.
• Previous research has limited understanding of the genetic profile of Ni(2+) in human cells.

Purpose of the Study:

• To investigate the gene expression profile induced by Ni(2+) in human primary monocytes.
• To identify novel target genes, pathways, and upstream regulators involved in Ni(2+)-elicited responses.
• To provide insights for diagnostic and therapeutic strategies related to nickel-induced pathologies.

Main Methods:

• Human monocytes were isolated and exposed to varying concentrations of Ni(2+).
• Transcriptome-wide gene expression analysis was performed using microarrays (>47,000 transcripts).
• Pathway and upstream regulator analyses were conducted, with validation by protein and cell surface markers.

Main Results:

• Ni(2+) significantly altered the expression of 1385 transcripts in a dose-dependent manner.
• Identified known targets (e.g., CCL20, PTGS2) and novel candidates (e.g., microRNAs, INSIG1, NAMPT).
• Detected significant changes in pathways related to immunity, inflammation, hypersensitivity, cancer, and neurological disorders.

Conclusions:

• This study is the first to systematically explore Ni(2+)-elicited responses in human primary monocytes at the transcriptome-wide level.
• New target genes, pathways, and upstream regulators implicated in nickel-induced pathologies were identified.
• Findings are relevant for developing diagnostic and therapeutic strategies for nickel-related diseases.