Homocysteine induces inflammatory transcriptional signaling in monocytes

• Published in: Frontiers in bioscience Vol. 18; no. 2; pp. 685 - 695
• Main Authors: Meng, Shu, Ciment, Stephen, Jan, Michael, Tran, Tran, Pham, Hung, Cueto, Ramon, Yang, Xiao-Feng, Wang, Hong
• Format: Journal Article
• Language: English
• Published: Singapore 01.01.2013
• Subjects: Cell Differentiation - drug effects; Cytokines - biosynthesis; Cytokines - pharmacology; Gene Expression Regulation - drug effects; Homocysteine - pharmacology; Humans; Hyperhomocysteinemia - metabolism; Interferon-gamma - pharmacology; Interleukin-10 - pharmacology; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Promoter Regions, Genetic - physiology; Signal Transduction - drug effects; Transcription Factors - metabolism
• ISSN: 1093-9946; 2768-6698; 1093-4715
• DOI: 10.2741/4131

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 pro-inflammatory 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 Hcy-induced 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.