Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Chungnam, Asan-si, Republic of Korea.
Department of ICT Environmental Health System, Graduate School, Soonchunhyang University, Chungnam, Asan-si, Republic of Korea.
Arch Pharm (Weinheim). 2021 Sep;354(9):e2100130. doi: 10.1002/ardp.202100130. Epub 2021 May 31.
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 α',β'-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.
Toll 样受体 (TLRs) 可以识别入侵微生物病原体的特定特征，并激活一系列下游信号，诱导炎症细胞因子、趋化因子和 I 型干扰素的分泌。TLRs 的激活触发两条下游信号通路：MyD88 和 TRIF 依赖性通路。为了评估 epoxomicin（一种从放线菌菌株中首次分离出的线性肽 α'，β'-环氧酮）的治疗潜力，我们研究了其对 TLR 信号通路信号转导的影响。Epoxomicin 抑制 TLR 激动剂诱导的 NF-kB 和 IRF3 的激活，降低干扰素诱导蛋白-10 的表达，并抑制 TLR 信号通路下游信号转导成分过表达诱导的 NF-kB 和 IRF3 的激活。这些结果表明，epoxomicin 可以调节 TLR 的 MyD88 和 TRIF 依赖性信号通路。因此，它可能有潜力成为治疗各种炎症性疾病的新型治疗药物。
