Grisha\u00a0Pirianov<\/a><\/p>\n\n\n\nAbstract<\/h2>\n\n\n\n
TLRs, including TLR4, play a crucial role in inflammatory-based diseases, and TLR4 has been identified as a therapeutic target for pharmacological intervention. In previous studies, we investigated the potential of FP7, a novel synthetic glycolipid active as a TLR4 antagonist, to inhibit haematopoietic and non-haematopoietic MyD88-dependent TLR4 pro-inflammatory signalling. The main aim of this study was to investigate the action of FP7 and its derivative FP12 on MyD88-independent TLR4 signalling in THP-1 derived macrophages. Western blotting, Ab array and ELISA approaches were used to explore the effect of FP7 and FP12 on TRIF-dependent TLR4 functional activity in response to LPS and other endogenous TLR4 ligands in THP-1 macrophages. A different kinetic in the inhibition of endotoxin-driven TBK1, IRF3 and STAT1 phosphorylation was observed using different LPS chemotypes. Following activation of TLR4 by LPS, data revealed that FP7 and FP12 inhibited TBK1, IRF3 and STAT1 phosphorylation which was associated with down-regulation IFN-\u03b2 and IP-10. Specific blockage of the IFN type one receptor showed that these novel molecules inhibited TRIF-dependent TLR4 signalling via IFN-\u03b2 pathways. These results add novel information on the mechanism of action of monosaccharide FP derivatives. The inhibition of the TRIF-dependent pathway in human macrophages suggests potential therapeutic uses for these novel TLR4 antagonists in pharmacological interventions on inflammatory diseases.<\/p>\n","protected":false},"excerpt":{"rendered":"
Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages Charys\u00a0Palmer,\u00a0Fabio A\u00a0Facchini, Richard PO\u00a0Jones, Frank\u00a0Neumann, Francesco\u00a0Peri, and\u00a0Grisha\u00a0Pirianov Abstract TLRs, including TLR4, play a crucial role in inflammatory-based diseases, and TLR4 has been identified as a therapeutic target for pharmacological intervention. In previous studies, we investigated the potential of<\/p>\n
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In previous studies, we investigated the potential ofRead More","og_url":"https:\/\/admin.innaxon.com\/index.php\/2023\/12\/18\/2023-synthetic-glycolipid-based-tlr4-antagonists-negatively-regulate-trif-dependent-tlr4-signalling-in-human-macrophages\/","og_site_name":"Innaxon Therapeutics","article_published_time":"2023-12-18T16:22:03+00:00","article_modified_time":"2023-12-18T16:28:39+00:00","author":"Innaxon","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Innaxon","Estimated reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/admin.innaxon.com\/index.php\/2023\/12\/18\/2023-synthetic-glycolipid-based-tlr4-antagonists-negatively-regulate-trif-dependent-tlr4-signalling-in-human-macrophages\/#article","isPartOf":{"@id":"https:\/\/admin.innaxon.com\/index.php\/2023\/12\/18\/2023-synthetic-glycolipid-based-tlr4-antagonists-negatively-regulate-trif-dependent-tlr4-signalling-in-human-macrophages\/"},"author":{"name":"Innaxon","@id":"https:\/\/admin.innaxon.com\/#\/schema\/person\/789de98f9e6bc1a104a5951de9b147af"},"headline":"2023 Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages","datePublished":"2023-12-18T16:22:03+00:00","dateModified":"2023-12-18T16:28:39+00:00","mainEntityOfPage":{"@id":"https:\/\/admin.innaxon.com\/index.php\/2023\/12\/18\/2023-synthetic-glycolipid-based-tlr4-antagonists-negatively-regulate-trif-dependent-tlr4-signalling-in-human-macrophages\/"},"wordCount":253,"keywords":["TLR4 antagonists"],"articleSection":["Literature"],"inLanguage":"en-GB"},{"@type":"WebPage","@id":"https:\/\/admin.innaxon.com\/index.php\/2023\/12\/18\/2023-synthetic-glycolipid-based-tlr4-antagonists-negatively-regulate-trif-dependent-tlr4-signalling-in-human-macrophages\/","url":"https:\/\/admin.innaxon.com\/index.php\/2023\/12\/18\/2023-synthetic-glycolipid-based-tlr4-antagonists-negatively-regulate-trif-dependent-tlr4-signalling-in-human-macrophages\/","name":"2023 Synthetic glycolipid-based TLR4 antagonists negatively regulate TRIF-dependent TLR4 signalling in human macrophages - 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