RAGE-Dependent Regulation of Calcium-Binding Proteins S100A8 and S100A9 in Human THP-1
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.
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S100A8/A9 is a marker of intestinal inflammation to predict the degree of inflammatory response.
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From Inhibition of SPI1 by ADAP Regulates S100A8/A9 Signaling in Macrophages to Control the Development of Colitis (2026) · cites this paper as [9]
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- Authors
- Eggers, K., Sikora, K., Lorenz, M., Taubert, T., Moobed, M., Baumann, G., Stangl, K., & Stangl, V.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- ORCID
- Venue
- Experimental and Clinical Endocrinology & Diabetes
- Publisher
- Georg Thieme Verlag KG
- Published
- 2011-04-06
- Volume
- 119
- Issue
- 06
- Pages
- 353-357
- ISSN
- 0947-7349 (ISSN-L)
- 1439-3646
- OpenAlex
- W2319809815
- Cited by
- 38
- References
- 0
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 4 · 2019: 3 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental and Clinical Endocrinology & Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- receptor for advanced glycation end products, S100A8, S100A9, advanced glycation end products, THP-1 cells, interleukin-6, TNF-α, inflammatory cytokines, atherosclerosis, gene expression regulation, calcium-binding proteins
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Calcium-Binding Proteins, Dose-Response Relationship, Drug, Humans, Leukemia, Receptors, Immunologic, Tumor Necrosis Factor-alpha, Signal Transduction, Interleukin-6, Gene Expression Regulation, Leukemic, Calgranulin A, Calgranulin B, Cell Line, Tumor, Mice
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