title: Homocysteine induces inflammatory transcriptional signaling in monocytes.
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 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.
authors.affiliation: Department of Pharmacology, Temple University School of Medicine, 3500 North Broad Street, 10th floor, Philadelphia, PA 19140, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Meng
authors.forename: Stephen
authors.initials: S
authors.lastname: Ciment
authors.forename: Michael
authors.initials: M
authors.lastname: Jan
authors.forename: Tran
authors.initials: T
authors.lastname: Tran
authors.forename: Hung
authors.initials: H
authors.lastname: Pham
authors.forename: Ramon
authors.initials: R
authors.lastname: Cueto
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D016207:Cytokines; D014157:Transcription Factors; D006710:Homocysteine; D016753:Interleukin-10; D007371:Interferon-gamma