cAMP ameliorates inflammation by modulation of macrophage receptor for advanced glycation end-products
Abstract
Clarification of the roles of PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) is indispensable for therapeutic strategies against various inflammatory diseases. RAGE (receptor for advanced glycation end-products) is one of the PRRs (pattern recognition receptors) and has been implicated in autoimmune and inflammatory diseases. Effective remedies targeting RAGE are required for the diseases. In the present study, we show that cAMP-induced modulation of the RAGE isoform in macrophages can control the inflammatory state in both in vitro and in vivo experimental conditions. The RAGE ligand S100B stimulated MCP-1 (monocyte chemoattractant protein-1) secretion from peritoneal macrophages, but cAMP elevation suppressed it by converting the RAGE isoform from a membrane-bound into a soluble form. This shedding is the result of ectodomain cleavage of mRAGE (membrane-bound RAGE) by MMP9 (matrix metalloproteinase 9). Furthermore, forskolin significantly inhibited peritoneal macrophage accumulation in a mouse S100B-induced peritonitis model. These results suggest that cAMP serves as a negative regulator of ligand–RAGE signalling and macrophage recruitment by mRAGE down-regulation and formation of decoys as soluble receptors. The present study should deepen our understanding of the pathogenesis of RAGE-mediated tissue derangement and provide new clues for overcoming RAGE-related inflammatory diseases.
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RAGE is not known to be related to oxytocin or oxytocin signalling.
“RAGE, a member of the immunoglobulin superfamily of pattern recognition receptors, is not known to be related to oxytocin or oxytocin signalling22–33.”
From Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice (2019) · cites this paper as [30]
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Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice
Yamamoto, Y., Liang, M., Munesue, S., Deguchi, K., Harashima, A., Furuhara, K., Yuhi, T., Zhong, J., Akther, S., Goto, H., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0325-6 · Cited by 171 · see citing works
Self-citation
- Authors
- Motoyoshi, S., Yamamoto, Y., Munesue, S., Igawa, H., Harashima, A., Saito, H., Han, D., Watanabe, T., Sato, H., & Yamamoto, H.
- Affiliations
- Kanazawa University (JP)
- Corresponding author
- Motoyoshi, So
- Yamamoto, Yasuhiko
- Munesue, Seiichi
- Igawa, Hirobumi
- Harashima, Ai
- Saito, Hidehito
- Han, Dong
- Watanabe, Takuo
- Yamamoto, Hiroshi
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2014-09-08
- Volume
- 463
- Issue
- 1
- Pages
- 75-82
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W1966518454
- Cited by
- 20
- References
- 48
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1 · 2016: 2 · 2015: 3
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (26450152, 25461335, 26860187, 24590375)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › S100 Proteins and Annexins
- Keywords
- cyclic AMP, receptor for advanced glycation end products, RAGE, macrophages, S100B, soluble RAGE, MMP-9, ectodomain shedding, MCP-1, peritonitis, inflammation, pattern recognition receptors, forskolin
- MeSH terms
- Receptor for Advanced Glycation End Products, Cyclic AMP, Animals, Inflammation, Receptors, Immunologic, Signal Transduction, Protein Structure, Tertiary, Macrophages, Peritoneal, Mice, Knockout, Chemokine CCL2, Matrix Metalloproteinase 9, Mice, Proteolysis, S100 Calcium Binding Protein beta Subunit
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