RAGE expression and NF-kappaB activation attenuated by extracellular domain of RAGE in human salivary gland cell line.
The receptor for advanced-glycation-end-products (RAGE) has been implicated as a pro-inflammatory factor in chronic inflammatory conditions such as diabetes mellitus and rheumatoid arthritis. The aim of this study was to investigate the inhibitory effect of the soluble-RAGE (sRAGE), the extracellular domain of RAGE, on RAGE expression and NF-kappaB translocation in human-salivary gland-cell-lines (HSG). Cells were stimulated with agonist S100A4, fusion protein of RAGE encompassing the extracellular domain of RAGE (ex-RAGE), ex-RAGE followed by S100A4, or S100A4 followed by ex-RAGE. Our study indicates that RAGE expression was highest at 150 microg/microl of S100A4 and efficiently down-regulated by 1.8-fold (P < 0.05) when ex-RAGE was incubated prior to agonist S100A4. RAGE protein was also consistently down-regulated by 20-40% with pre-incubation of ex-RAGE. More importantly, nuclear translocation of p65 and p52 of NF-kappaB by S100A4 was inhibited in the presence of ex-RAGE, confirming anti-inflammatory function of ex-RAGE. In conclusion, ex-RAGE down-regulates RAGE expression and inhibits p65 and p52 activation in HSG, providing evidence that ex-RAGE functions as a "decoy" to RAGE-ligand interaction and thus potentially dampening inflammatory conditions.
Chuong
Christopher
C
Oral Surgery and Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Katz
Joseph
J
Pauley
Kaleb M
KM
Bulosan
Marievic
M
Cha
Seunghee
S
D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000494:pharmacology*; D012469:Salivary Glands / Q000166:cytology*; D051996:Transcription Factor RelA / Q000378:metabolism
D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D021122:Protein Subunits; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D051996:Transcription Factor RelA; C077591:S100A4 protein, human