RGD Reference Report - Septic shock is associated with receptor for advanced glycation end products ligation of LPS. - Rat Genome Database

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Septic shock is associated with receptor for advanced glycation end products ligation of LPS.

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 
Citation: Yamamoto Y, etal., J Immunol. 2011 Mar 1;186(5):3248-57. Epub 2011 Jan 26.
RGD ID: 6767566
Pubmed: PMID:21270403   (View Abstract at PubMed)
DOI: DOI:10.4049/jimmunol.1002253   (Journal Full-text)

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-alpha secretion from peritoneal macrophages and an NF-kappaB 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-alpha, 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
toxic shock syndrome  ISOAger (Mus musculus)6767566; 6767566 RGD 
toxic shock syndrome  IAGP 6767566 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Mus musculus)
Ager  (advanced glycosylation end product-specific receptor)

Genes (Homo sapiens)
AGER  (advanced glycosylation end-product specific receptor)


Additional Information