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  1. Xiao Huang1,
  2. Ren Gong1,
  3. Xiao-feng Yang2,
  4. Hong Wang2,
  5. Xiao-shu Cheng1,
  6. Xiao Huang2
  1. 1Department of Cardiology, Second hospital of Nanchang University, Nan Chang, Jiang Xi, China 330006
  2. 2Department of Pharmacology and Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA


    Objectives Nuclear factor-κB (NF-κB) family are critical regulators in immunity, stress responses, apoptosis and differentiation, however, tissue NF-κB metabolism and their relevance to methylation status remain unknown.

    Methods We examined gene expression profiles of 5 NF-κB transcription factors, 6 inhibitory IκB proteins (I-κB), 3 IκB kinase (IKK) complex and 24 pathway components in NF-κB signalling pathway. Data-base mining of NF-κB family members and conponnets mRNA expressions are accomplished by querying GEO DataSets profiles under inflammation cytokine stimuli, hypomethylation status, and homocysteine treat. We analysed correlations between gene expression, S-adenosylhomocysteine (SAH), and S-adenosylmethion ine (SAM) levels, and SAM/SAH ratios in 7 mouse tissues.

    Results Our results showed that (1) NF-κB family members and pathway components have different expression levels in different tissues, and high expression in mouse, but inactive in human in normal condition; (2) Vascular system has lower response to NF-κB activity; (3) Tissues can be divided into 3 tiers according to essential molecular of NF-κB canonical and non-canonical pathway expression level in normal condition; (4) Canonical pathway is activated immediately after inflammatory cytokine TNF-α, IL-1 stimuli, but non-canonical pathway is up-regulated until 4 h treatment; (5) Lymphotoxin β/LIGHT has no effect on NF-κB family members and components expressions at 4 h; (6) Sca1+ subset endothelial progenitor cells has lower NF-κB family members and components expressions level than Sca1- subset endothelial progenitor cells; (7) Most of NF-κB family members and components expressions are down-regulated by hypomethylation status; (8) Most of NF-κB family members and components expressions are down-regulated by acute homocystein treat in different cell type.

    Conclusions These new results provide an insight on the roles of NF-κB family members and components in tissues and cross talk between canonical and non-canonical pathway in different cell type, and its relevance to methylation. Our study is the first to make a model of specific tissue gene expression profiles of NF-κB and regulation of tissue methylation.

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