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ACS Chem Biol. 2014 Jan 17;9(1):247-57. doi: 10.1021/cb400740c. Epub 2013 Oct 29.

Unbiased screening of marine sponge extracts for anti-inflammatory agents combined with chemical genomics identifies girolline as an inhibitor of protein synthesis.

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1
Department of Pediatrics, British Columbia Children's Hospital and Child & Family Research Institute, University of British Columbia , Vancouver, British Columbia V5Z 4H4, Canada.

Abstract

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.

PMID:
24117378
PMCID:
PMC4371607
DOI:
10.1021/cb400740c
[Indexed for MEDLINE]
Free PMC Article
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