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Tussilagone inhibits dendritic cell functions via induction of heme oxygenase-1.

Abstract
Sesquiterpenoid tussilagone (TUS) has a variety of pharmacological activities, such as anti-oxidant, anti-cancer, and anti-inflammatory activities. In this study, we investigated the effects of TUS on dendritic cell (DC) functions and the underlying mechanisms. TUS inhibited lipopolysaccharide (LPS)-induced activation of DCs, as shown by decrease in surface molecule expression, cytokine production, cell migration, and allo-T cell activation. In addition, TUS inhibited LPS-induced activation of NF-κB, MAPKs, and IRF-3 signalings in DCs, although it did not directly affect kinase activities of IRAK1/4, TAK1, and IKK, which suggests that TUS might indirectly inhibit TLR signaling in DCs. As a critical mechanism, we showed that TUS activated heme oxygenase-1 (HO-1), which degrades heme to immunosuppressive products, such as carbon monoxide and bilirubin. HO-1 inhibitor reversed the inhibitory activity of TUS in DCs. In conclusion, this study suggests that TUS inhibits DC function through the induction of HO-1.
AuthorsYunsoo Park, Hwa Sun Ryu, Hong Kyung Lee, Ji Sung Kim, Jieun Yun, Jong Soon Kang, Bang Yeon Hwang, Jin Tae Hong, Youngsoo Kim, Sang-Bae Han
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 22 Issue 2 Pg. 400-8 (Oct 2014) ISSN: 1878-1705 [Electronic] Netherlands
PMID25091622 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • Cytokines
  • Membrane Proteins
  • Reactive Oxygen Species
  • Sesquiterpenes
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Nitric Oxide
  • tussilagone
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Protein Kinases
Topics
  • Animals
  • Cytokines (genetics, metabolism)
  • Dendritic Cells (drug effects, immunology, metabolism)
  • Female
  • Heme Oxygenase-1 (biosynthesis)
  • Lymphocyte Culture Test, Mixed
  • Membrane Proteins (biosynthesis)
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nitric Oxide (metabolism)
  • Protein Kinases (metabolism)
  • Reactive Oxygen Species (metabolism)
  • Sesquiterpenes (pharmacology)
  • Spleen (cytology)
  • T-Lymphocytes (drug effects, immunology)
  • Toll-Like Receptor 4 (antagonists & inhibitors)

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