biostudies-literatureFung SYNHGRI NIH HHSNIGMS NIH HHSCIHR247-57https://www.ebi.ac.uk/biostudies/studies/S-EPMC4371607biostudies-literatureUnknown9(1)Toll-like receptors (TLRs) play a critical role in innate immunity, but activation of TLR signaling pathways is also associated with many harmful inflammatory diseases. Identification of novel anti-inflammatory molecules targeting TLR signaling pathways is central to the development of new treatment approaches for acute and chronic inflammation. We performed high-throughput screening from crude marine sponge extracts on TLR5 signaling and identified girolline. We demonstrated that girolline inhibits signaling through both MyD88-dependent and -independent TLRs (i.e., TLR2, 3, 4, 5, and 7) and reduces cytokine (IL-6 and IL-8) production in human peripheral blood mononuclear cells and macrophages. Using a chemical genomics approach, we identified Elongation Factor 2 as the molecular target ofACS chemical biologyUnbiased screening of marine sponge extracts for anti-inflammatory agents combined with chemical genomics identifies girolline as an inhibitor of protein synthesis.PMC43716071R01HG005084-01A1MOP-57830R01 GM104975R01 HG0050841R01GM104975-01Woods KFung SYPiotrowski JSVictor REBoone CLi SCMyers CLde Voogd NJSofiyev VDeshpande RHirschfeld AFAndersen RJSchneiderman JTurvey SEfalseUnbiased screening of marine sponge extracts for anti-inflammatory agents combined with chemical genomics identifies girolline as an inhibitor of protein synthesis.Toll-like receptors (TLRs) play a critical role in innate immunity, but activation of TLR signaling pathways is also associated with many harmful inflammatory diseases. Identification of novel anti-inflammatory molecules targeting TLR signaling pathways is central to the development of new treatment approaches for acute and chronic inflammation. We performed high-throughput screening from crude marine sponge extracts on TLR5 signaling and identified girolline. We demonstrated that girolline inhibits signaling through both MyD88-dependent and -independent TLRs (i.e., TLR2, 3, 4, 5, and 7) and reduces cytokine (IL-6 and IL-8) production in human peripheral blood mononuclear cells and macrophages. Using a chemical genomics approach, we identified Elongation Factor 2 as the molecular target of2014-01-01T00:00:00Z2014 Jan2025-04-18T19:18:19.691Z2019-03-27T01:48:41ZS-EPMC43716072411737810.1021/cb400740c