Fung, Shan-Yu Sofiyev, Vladimir Schneiderman, Julia Hirschfeld, Aaron F. Victor, Rachel E. Woods, Kate Piotrowski, Jeff S. Deshpande, Raamesh Li, Sheena C. J. de Voogd, Nicole Myers, Chad L. Boone, Charlie Andersen, Raymond J. Turvey, Stuart E. Unbiased 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 of girolline, which inhibits protein synthesis at the elongation step. Together these data identify the sponge natural product girolline as a potential anti-inflammatory agent acting through inhibition of protein synthesis. crude marine sponge extracts;girolline;chemical genomics approach;IL;TLR;Elongation Factor 2;protein synthesis;Marine Sponge Extracts;Chemical Genomics Identifies Girolline 2014-01-17
    https://acs.figshare.com/articles/journal_contribution/Unbiased_Screening_of_Marine_Sponge_Extracts_for_Anti_inflammatory_Agents_Combined_with_Chemical_Genomics_Identifies_Girolline_as_an_Inhibitor_of_Protein_Synthesis/2331193
10.1021/cb400740c.s001