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Archiv der Pharmazie
Kim, SY;Shin, S;Kwon, M;Youn, D;Sung, NJ;Kim, NH;Park, SA;Youn, HS;
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-kB and IRF3 induced by TLR agonists, decreased the expression of interferon-inducible protein-10, and inhibited the activation of NF- kB 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.