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Suppression of the TRIF‐dependent signaling pathway of TLRs by epoxomicin
Author(s) -
Kim Su Y.,
Shin Seokwon,
Kwon Minji,
Youn Daniel,
Sung Nam J.,
Kim Na H.,
Park SinAye,
Youn HyungSun
Publication year - 2021
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.202100130
Subject(s) - trif , signal transduction , irf3 , biology , microbiology and biotechnology , nf κb , receptor , toll like receptor , biochemistry , innate immune system
Toll‐like receptors (TLRs) can recognize specific signatures of invading microbial pathogens and activate a cascade of downstream signals to induce the secretion of inflammatory cytokines, chemokines, and type I interferons. The activation of TLRs triggers two downstream signaling pathways: the MyD88‐ and the TRIF‐dependent pathways. To evaluate the therapeutic potential of epoxomicin, a member of the linear peptide αʹ,βʹ‐epoxyketone first isolated from an actinomycetes strain, we examined its effects on signal transduction via TLR signaling pathways. Epoxomicin inhibited the activation of NF‐ k B and IRF3 induced by TLR agonists, decreased the expression of interferon‐inducible protein‐10, and inhibited the activation of NF‐ k B and IRF3 induced by overexpression of downstream signaling components of TLR signaling pathways. These results suggest that epoxomicin can regulate both the MyD88‐ and TRIF‐dependent signaling pathways of TLRs. Thus, it might have potential as a new therapeutic drug for a variety of inflammatory diseases.