CpG promoter methylation status is not a prognostic indicator of gene expression in beryllium challenge.

ABSTRACT: Individuals exposed to beryllium (Be) may develop Be sensitization (BeS) and progress to chronic beryllium disease (CBD). Recent studies with other metal antigens suggest epigenetic mechanisms may be involved in inflammatory disease processes, including granulomatous lung disorders and that a number of metal cations alter gene methylation. The objective of this study was to determine if Be can exert an epigenetic effect on gene expression by altering methylation in the promoter region of specific genes known to be involved in Be antigen-mediated gene expression. To investigate this objective, three macrophage tumor mouse cell lines known to differentially produce tumor necrosis factor (TNF)-?, but not interferon (IFN)-?, in response to Be antigen were cultured with Be or controls. Following challenges, ELISA were performed to quantify induced TNF? and IFN? expression. Bisulfate-converted DNA was evaluated by pyrosequencing to quantify CpG methylation within the promoters of TNF? and IFN?. Be-challenged H36.12J cells expressed higher levels of TNF? compared to either H36.12E cells or P388D.1 cells. However, there were no variations in TNF? promoter CpG methylation levels between cell lines at the six CpG sites tested. H36.12J cell TNF? expression was shown to be metal-specific by the induction of significantly more TNF? when exposed to Be than when exposed to aluminum sulfate, or nickel (II) chloride, but not when exposed to cobalt (II) chloride. However, H36.12J cell methylation levels at the six CpG sites examined in the TNF? promoter did not correlate with cytokine expression differences. Nonetheless, all three cell lines had significantly more promoter methylation at the six CpG sites investigated within the IFN? promoter (a gene that is not expressed) when compared to the six CpG sites investigated in the TNF? promoter, regardless of treatment condition (p?

SUBMITTER: Tooker BC 

PROVIDER: S-EPMC4907869 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature