title: 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.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Yunsoo
authors.initials: Y
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Hwa Sun
authors.initials: HS
authors.lastname: Ryu
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, South Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, South Korea.
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea. Electronic address: shan@cbnu.ac.kr.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007959:Lymphocyte Culture Test, Mixed; D008565:Membrane Proteins / Q000096:biosynthesis*; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; C054337:tussilagone; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D011494:Protein Kinases
keywords: Dendritic cells; Heme oxygenase-1; MAPKs; NF-κB; Tussilagone