Title page for etd-0119112-150954


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URN etd-0119112-150954
Author Wen-chi Wei
Author's Email Address jackwei@gate.sinica.edu.tw
Statistics This thesis had been viewed 5567 times. Download 533 times.
Department Marine Biotechnology and Resources
Year 2011
Semester 1
Degree Ph.D.
Type of Document
Language English
Title The study of marine excavatolide diterpenoids on bioactivities: Lessons learned from dendritic cells, dermatitis and type 1 diabetes in murine models
Date of Defense 2012-01-03
Page Count 85
Keyword
  • excavatolide B
  • corals
  • dendritic cells
  • briarane-type diterpenoids
  • Abstract Corals are marine animals from the class Anthozoa and are widely distributed in
    tropical and subtropical seawaters. They are considered as an important source of lead
    compounds for drug discovery. For evaluating the medicinal activities of briarane-type
    diterpenoids (BrDs) from marine coral Briareum excavatum, the regulation of a group of briarane-type diterpenoids (BrDs) on dendritic cell (DC) function, TPA-induced dermatitis and type 1 diabetes was investigated. The results show that the BrD excavatolide K (BrD2) remarkably suppressed the activation of human DCs, especially the expression of IL-12 p40. This inhibitory effect was mediated apparently by interference with the rictor-mTOR/Akt-mediated signaling network, resulting in persistent-phase activation of NF-kB and Erk1/2 signalings. In addition, the 8,17-epoxide of BrDs was observed to play a crucial role in inhibition of IL-12 p40 expression. Replacement of the C-12 hydroxyl group with longer esters in BrDs gradually decreased this inhibitory activity in human DCs. BrD excavatolide B (BrD1) effectively suppressed the capacity of mouse bone marrow-derived DCs to induce an antigen-specific Th1, response via the inhibition of IL-12 expression. Moreover, excavatolide B prevented the onset of autoreactive T cell-mediated diabetes in NOD/SCID mice. Furthermore, excavatolide B remarkably suppressed TPA-induced vascular permeability and edema in test skin tissues. At the biochemical level, excavatolide B inhibited TPA-induced expression of cyclooxygenase-2, inducible nitric oxide synthase and matrix metalloproteinase-9, the key indicators of cutaneous inflammation. This inhibition is apparently mediated by interference with the Akt/NF-kB-mediated signaling network. Together, these studies demonstrate that BrDs from specific marine corals can effectively regulate defined molecular and cellular functions of dendritic cells, suppress TPA-induced dermatitis, and prevent type 1 diabetes in murine models suggesting that BrDs may warrant further investigation as natural immunomodulatory agents or therapeutics.
    Advisory Committee
  • Fang-Rong Chang - chair
  • Lie-Fen Shyur - co-chair
  • David Wang - co-chair
  • Ning-Sun Yang - advisor
  • Jyh-Horng Sheu - advisor
  • Files
  • etd-0119112-150954.pdf
  • Indicate in-campus at 3 year and off-campus access at 3 year.
    Date of Submission 2012-01-19

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