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http://purl.uniprot.org/citations/22804476http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22804476http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22804476http://www.w3.org/2000/01/rdf-schema#comment"Interactions between danger-associated molecular patterns (DAMP) and pathogen-associated molecular patterns (PAMP) and pattern recognition receptors such as Toll-like receptors (TLRs) are critical for the regulation of the inflammatory process via activation of nuclear factor-κB (NF-κB) and cytokine secretion. In this report, we investigated the capacity of lipopolysaccharide (LPS) -free S100A9 (DAMP) protein to activate human and mouse cells compared with lipoprotein-free LPS (PAMP). First, we showed that LPS and S100A9 were able to increase NF-κB activity followed by increased cytokine and nitric oxide (NO) secretion both in human THP-1 cells and in mouse bone marrow-derived dendritic cells. Surprisingly, although S100A9 triggered a weaker cytokine response than LPS, we found that S100A9 more potently induced IκBα degradation and hence NF-κB activation. Both the S100A9-induced response and the LPS-induced response were completely absent in TLR4 knockout mice, whereas it was only slightly affected in RAGE knockout mice. Also, we showed that LPS and S100A9 NF-κB induction were strongly reduced in the presence of specific inhibitors of TLR-signalling. Chloroquine reduced S100A9 but not LPS signalling, indicating that S100A9 may need to be internalized to be fully active as a TLR4 inducer. This was confirmed using A488-labelled S100A9 that was internalized in THP-1 cells, showing a raise in fluorescence after 30 min at 37°. Chloroquine treatment significantly reduced the fluorescence. In summary, our data indicate that both human and mouse S100A9 are TLR4 agonists. Importantly, S100A9 induced stronger NF-κB activation albeit weaker cytokine secretion than LPS, suggesting that S100A9 and LPS activated NF-κB in a qualitatively distinct manner."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2567.2012.03619.x"xsd:string
http://purl.uniprot.org/citations/22804476http://purl.org/dc/terms/identifier"doi:10.1111/j.1365-2567.2012.03619.x"xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Roth J."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Roth J."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Leanderson T."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Leanderson T."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Riva M."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Riva M."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Vogl T."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Vogl T."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Bjoerk P."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Bjoerk P."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Hancz D."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Hancz D."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Ivars F."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Ivars F."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Kaellberg E."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/author"Kaellberg E."xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/name"Immunology"xsd:string
http://purl.uniprot.org/citations/22804476http://purl.uniprot.org/core/name"Immunology"xsd:string