Homocysteine induces inflammatory transcriptional signaling in monocytes

Shu Meng, Stephen Ciment, Michael Jan, Tran Tran, Hung Pham, Ramon Cueto, Xiao Feng Yang, Hong Wang

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease. Here, we studied transcriptional regulation in homocysteine (Hcy)- induced gene expression in monocytes (MC). We identified 11 Hcy-induced genes, 17 anti-inflammatory cytokine interleukin 10-induced, 8 pro-inflammatory cytokine interferon gamma (IFN gamma)-induced and 8 proinflammatory cytokine tumor necrosis factor alpha (TNF alpha)-induced genes through literature search. Binding frequency of 36 transcription factors (TFs) implicated in inflammation and MC differentiation were analyzed within core promoter regions of identified genes, and classified into 3 classes based on the significant binding frequency to the promoter of Hcy-induced genes. Class 1 TFs exert high significant binding frequency in Hcy-induced genes. Class 2 and 3 TFs have low and no significant binding frequency, respectively. Class 1 TF binding occurrence in Hcyinduced genes is similar to that in IFN gamma -induced genes, but not that in TNF alpha -induced. We conclude that Hcy is a pro-inflammatory amino acid and induces inflammatory transcriptional signal pathways mediated by class 1 TF. We term class 1 TF as putative Hcy-responsive TFs.

Original languageEnglish (US)
Pages (from-to)685-695
Number of pages11
JournalFrontiers in Bioscience
Volume18
Issue number2
DOIs
StatePublished - Jan 1 2013

Keywords

  • Gene Expression
  • Homocysteine
  • Inflammation
  • Monocyte Differentiation
  • Transcription Factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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