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Suppressive effects of dehydrocostus lactone on the toll-like receptor signaling pathways

Kim, SY;Heo, S;Kim, SH;Kwon, M;Sung, NJ;Ryu, AR;Lee, MY;Park, SA;Youn, HS;

Toll-like receptors (TLRs) are a group of pattern-recognition receptors (PRRs) that are at the core of innate and adaptive immune responses. TLRs activation triggers the activation of two downstream signaling pathways, the myeloid differential factor 88 (MyD88)- and toll-interleukin-1 receptor domain-containing adapter inducing interferon- (TRIF)-dependent pathways. To evaluate the therapeutic potential of DHL, a natural sesquiterpene lactone derived from Inulahelenium L. and Saussurea lappa, we examined its effect on signal transduction via the TLR signaling pathways. DHL inhibited the activation of nuclear factor-B (NF-B) and interferon regulatory factor 3 (IRF3), the representative transcription factors involved in the inflammatory response, induced by TLR agonists, as well as the expression of cyclooxygenase-2 and interferon inducible protein-10. DHL also inhibited the activation of NF-B and IRF3 induced by the overexpression of downstream signaling components of the TLRs signaling pathways. All results suggest that DHL might become a new therapeutic drug for a variety of inflammatory diseases. Copyright 2019 Elsevier B.V. All rights reserved.

  • PubMed ID: 31812722