10.1021/cb400740c.s001
Shan-Yu Fung
Shan-Yu
Fung
Vladimir Sofiyev
Vladimir
Sofiyev
Julia Schneiderman
Julia
Schneiderman
Aaron F. Hirschfeld
Aaron F.
Hirschfeld
Rachel E. Victor
Rachel E.
Victor
Kate Woods
Kate
Woods
Jeff S. Piotrowski
Jeff S.
Piotrowski
Raamesh Deshpande
Raamesh
Deshpande
Sheena C. Li
Sheena C.
Li
Nicole J. de Voogd
Nicole
J. de Voogd
Chad L. Myers
Chad L.
Myers
Charlie Boone
Charlie
Boone
Raymond J. Andersen
Raymond J.
Andersen
Stuart E. Turvey
Stuart E.
Turvey
Unbiased Screening of Marine Sponge Extracts for Anti-inflammatory
Agents Combined with Chemical Genomics Identifies Girolline as an
Inhibitor of Protein Synthesis
American Chemical Society
2014
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 00:00:00
Journal contribution
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
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.