title: Saucerneol D inhibits dendritic cell activation by inducing heme oxygenase-1, but not by directly inhibiting toll-like receptor 4 signaling.
abstract: BACKGROUND
  Saururus chinensis is a medicinal plant used to treat jaundice, pneumonia, edema, fever, and several inflammatory diseases. Saucerneol D (SD), a lignan constituent of this plant, has antioxidant, anti-asthmatic, and anti-inflammatory activities. SD has been previously reported to inhibit the pro-inflammatory responses of RAW264.7 cells and primary mast cells. In this study, we investigated the effect of SD on the functions of dendritic cells (DCs).
  
  
  METHODS
  SD was isolated from methanol extract of the roots of S. chinensis. Bone marrow-derived DCs were used as target cells. The effects of SD on the following DC functions were examined: surface molecule expression, cytokine expression, migration, allogenic T cell activation, heme oxygenase-1 expression, and Toll-like receptor 4 signaling.
  
  
  RESULTS
  In lipopolysaccharide (LPS)-treated DCs, SD inhibited the expression of cell surface molecules (MHC I/II, CD40, CD80, and CD86), the production of inflammatory mediators (nitric oxide, IL-12, IL-1β, and TNF-α), and allogenic T cell activation capacity. SD also inhibited DC migration toward MIP-3β by down-regulating CCR7 expression. SD attenuated LPS-induced activation of NF-κB and MAPK signaling in DCs, but did not directly inhibit kinase activities of IRAK1, IRAK4, TAK1, or IKKβ in enzymatic assays. SD did not inhibit LPS binding to myeloid differentiation protein-2, co-receptor of TLR4. SD increased the production of reactive oxygen species, Nrf-2, and heme oxygenase (HO)-1, which degrades the heme to immunosuppressive carbon monoxide and biliverdin, which may underlie the anti-inflammatory effects in SD-treated DCs.
  
  
  CONCLUSIONS
  Taken together, these data suggest that SD suppresses LPS-induced activation of DCs through the induction of HO-1, but not by directly affecting Toll-like receptor 4 signaling.
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Hwa Sun
authors: HS
authors: Ryu
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Hong Kyung
authors: HK
authors: Lee
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Ji Sung
authors: JS
authors: Kim
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Yong Guk
authors: YG
authors: Kim
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Minji
authors: M
authors: Pyo
authors: Korea Research Institute of Bioscience and Biotechnology, Ochang, Chungbuk 363-883, South Korea.
authors: Jieun
authors: J
authors: Yun
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Bang Yeon
authors: BY
authors: Hwang
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Jin Tae
authors: JT
authors: Hong
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea.
authors: Youngsoo
authors: Y
authors: Kim
authors: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 362-763, South Korea. Electronic address: shan@chungbuk.ac.kr.
authors: Sang-Bae
authors: SB
authors: Han
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D017705:Lignans / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018517:Plant Roots / Q000737:chemistry; D032134:Saururaceae / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D017705:Lignans; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C561428:saucerneol D; D051547:Heme Oxygenase-1
keywords: Dendritic cells; Heme oxygenase-1; Inflammation; Saucerneol D; TLR4