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.