Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
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Exp. Clin. Endocrinol. Diabetes · Jun 2011
RAGE-dependent regulation of calcium-binding proteins S100A8 and S100A9 in human THP-1.
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. ⋯ 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.