Septic Shock Is Associated with Receptor for Advanced Glycation End Products Ligation of LPS
Open accessAbstract
Septic shock is a severe systemic response to bacterial infection. Receptor for advanced glycation end products (RAGE) plays a role in immune reactions to recognize specific molecular patterns as pathogen recognition receptors. However, the interaction between LPS, the bioactive component of bacterial cell walls, and RAGE is unclear. In this study, we found direct LPS binding to RAGE by a surface plasmon resonance assay, a plate competition assay, and flow cytometry. LPS increased TNF-α secretion from peritoneal macrophages and an NF-κB promoter-driven luciferase activity through RAGE. Blood neutrophils and monocytes expressed RAGE, and TLR2 was counterregulated in RAGE−/− mice. After LPS injection, RAGE+/+ mice showed a higher mortality, higher serum levels of IL-6, TNF-α, high mobility group box 1, and endothelin-1, and severe lung and liver pathologies compared with RAGE−/− mice without significant differences in plasma LPS level. Administration of soluble RAGE significantly reduced the LPS-induced cytokine release and tissue damage and improved the LPS-induced lethality even in RAGE−/− as well as RAGE+/+ mice. The results thus suggest that RAGE can associate with LPS and that RAGE system can regulate inflammatory responses. Soluble RAGE would be a therapeutic tool for LPS-induced septic shock.
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High doses of endotoxin in blood cause a 'cytokine storm', septic shock and death, via activating TLR4, RAGE and caspases.
“High doses of endotoxin in blood (endotoxemia) cause a ‘cytokine storm’, septic shock and death, via activating TLR4, RAGE and caspases [16, 18, 20, 21].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [21]
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 [27]
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- Authors
- Yamamoto, Y., Harashima, A., Saito, H., Tsuneyama, K., Munesue, S., Motoyoshi, S., Han, D., Watanabe, T., Asano, M., Takasawa, S., Okamoto, H., Shimura, S., Karasawa, T., Yonekura, H., & Yamamoto, H.
- Affiliations
- Kanazawa University (JP)
- University of Toyama (JP)
- Nara Medical University (JP)
- Tohoku University (JP)
- Kanazawa Medical University (JP)
- Corresponding author
- Yamamoto, Yasuhiko
- Harashima, Ai
- Saito, Hidehito
- Munesue, Seiichi
- Motoyoshi, So
- Han, Dong
- Watanabe, Takuo
- Yamamoto, Hiroshi
- ORCID
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-01
- Volume
- 186
- Issue
- 5
- Pages
- 3248-3257
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2133223253
- Cited by
- 207
- References
- 44
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 8 · 2023: 12 · 2022: 27 · 2021: 15 · 2020: 11 · 2019: 15 · 2018: 7 · 2017: 12 · 2016: 15 · 2015: 9 · 2014: 16 · 2013: 21 · 2012: 20
- FWCI
- 11.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (22591096, 16790183, 17590241, 16570113, 23659430)
- 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
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- septic shock, receptor for advanced glycation end products, RAGE, lipopolysaccharide, LPS binding, pathogen recognition receptors, TNF-α, NF-κB signaling, TLR2, soluble RAGE, cytokine production, inflammation, RAGE knockout mice, sepsis mortality, interleukin-6, HMGB1, endothelin-1
- MeSH terms
- Receptor for Advanced Glycation End Products, Amino Acid Sequence, Animals, Binding, Competitive, Humans, Ligands, Lipopolysaccharides, Male, Molecular Sequence Data, Protein Binding, Receptors, Immunologic, Shock, Septic, Tumor Necrosis Factor-alpha, Signal Transduction, Survival Analysis, NF-kappa B, Glycation End Products, Advanced, Mice, Knockout, Inflammation Mediators, Cell Line, Tumor, Mice, Rats
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