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DOI: 10.1055/s-0030-1268426
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
RAGE-Dependent Regulation of Calcium-Binding Proteins S100A8 and S100A9 in Human THP-1
Publikationsverlauf
received 31.07.2010
first decision 01.10.2010
accepted 27.10.2010
Publikationsdatum:
06. April 2011 (online)
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Abstract
Proinflammatory cell activation via the receptor for advanced glycation end products (RAGE) pathway may play a central pathogenetic role in atherosclerosis. Since S100A8/A9 was recently identified as ligand of RAGE, we determined the effects of proinflammatory cytokines on RAGE-mediated induction of gene expression of S100A8 and S100A9. mRNA levels of S100A8 and S100A9 were upregulated following cytokine stimulation with IL-6 (1, 10, 100 ng/ml) or TNFα (10 ng/ml) in human THP-1 cells. Preincubation of cells with 2000 ng/ml AGE (advanced glycation end products) before cytokine stimulation resulted in upregulation of RAGE. Pretreatment of THP-1 with AGE followed by stimulation with IL-6 (10 ng/ml) or TNFα (10 ng/ml) further increased S100A8 and S100A9 mRNA expression and S100A8/A9 release into cell culture supernatant, as compared to pretreatment with non-glycated albumin as control. Binding of AGE to RAGE was blocked with a neutralizing anti-RAGE antibody. Normal mouse IgG served as control. Cytokine-stimulated induction of S100A8 and S100A9 mRNA levels as well as of S100A8/A9 release after preincubation of cells with AGE were significantly suppressed by RAGE blockade, indicating a RAGE-dependent pathway of AGE-mediated S100A8/A9 expression.The cytokine-induced potentiated S100A8 and S100A9 expression under conditions with a high AGE burden is able to aggravate proinflammatory conditions via activation of the RAGE pathway.
Key words
S100 proteins - glycation/AGE - RAGE - inflammation - diabetes
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Correspondence
Dr. med. K. Eggers
Med. Klinik mit Schwerpunkt
Kardiologie und Angiologie
Universitätsmedizin Berlin
Charité Campus Mitte
Charitéplatz 1
D – 10117 Berlin
Germany
Telefon: +49/30/450 613 236
Fax: +49/30/450 513 915
eMail: kai.eggers@charite.de