Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 78, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2019.106075
Keywords
Dehydrocostus lactone; Toll-like receptor; MyD88; TRIF; IRF3
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Funding
- Soonchunhyang University Research Fund, South Korea
- National Research Foundation of South Korea (NRF) - Ministry of Education [2017R1D1A1B03031534]
- National Research Foundation of Korea [2017R1D1A1B03031534] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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-beta (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-kappa B (NF-kappa 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-KB 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.
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