Open Access

Homocysteine induces inflammatory transcriptional signaling in monocytes

Shu Meng1,Stephen Ciment1,Michael Jan1,Tran Tran1,Hung Pham1,Ramon Cueto1,Xiao-Feng Yang1,Hong Wang1,*
Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA, 19140, USA
DOI: 10.2741/4131 Volume 18 Issue 2, pp.685-695
Published: 01 January 2013
*Corresponding Author(s):  
Hong Wang

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.

Key words

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

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Shu Meng, Stephen Ciment, Michael Jan, Tran Tran, Hung Pham, Ramon Cueto, Xiao-Feng Yang, Hong Wang. Homocysteine induces inflammatory transcriptional signaling in monocytes. Frontiers in Bioscience-Landmark. 2013. 18(2); 685-695.