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RAGE expression and NF‐κB activation attenuated by extracellular domain of RAGE in human salivary gland cell line
Author(s) -
Chuong Christopher,
Katz Joseph,
Pauley Kaleb M.,
Bulosan Marievic,
Cha Seunghee
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21873
Subject(s) - rage (emotion) , glycation , receptor , extracellular , hmgb1 , ex vivo , endocrinology , agonist , chemistry , medicine , biology , microbiology and biotechnology , in vitro , biochemistry , neuroscience
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‐κB 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 µg/µl 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‐κB 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. J. Cell. Physiol. 221: 430–434, 2009. © 2009 Wiley‐Liss, Inc.