PUBLICATION

Vibsanin B Preferentially Targets HSP90β, Inhibits Interstitial Leukocyte Migration, and Ameliorates Experimental Autoimmune Encephalomyelitis

Authors
Ye, B.X., Deng, X., Shao, L.D., Lu, Y., Xiao, R., Liu, Y.J., Jin, Y., Xie, Y.Y., Zhao, Y., Luo, L.F., Ma, S., Gao, M., Zhang, L.R., He, J., Zhang, W.N., Chen, Y., Xia, C.F., Deng, M., Liu, T.X., Zhao, Q.S., Chen, S.J., Chen, Z.
ID
ZDB-PUB-150327-3
Date
2015
Source
Journal of immunology (Baltimore, Md. : 1950)   194(9): 4489-97 (Journal)
Registered Authors
Chen, Yi, Chen, Zhu, Deng, Min, Jin, Yi, Liu, Ting Xi, Zhao, Yan
Keywords
none
MeSH Terms
  • Animals
  • Cell Line
  • Cell Movement/drug effects*
  • Central Nervous System/drug effects
  • Central Nervous System/immunology
  • Central Nervous System/metabolism
  • Central Nervous System/pathology
  • Diterpenes/administration & dosage
  • Diterpenes/pharmacology*
  • Encephalomyelitis, Autoimmune, Experimental/drug therapy
  • Encephalomyelitis, Autoimmune, Experimental/immunology*
  • Encephalomyelitis, Autoimmune, Experimental/metabolism*
  • Encephalomyelitis, Autoimmune, Experimental/pathology
  • Female
  • HSP90 Heat-Shock Proteins/antagonists & inhibitors
  • HSP90 Heat-Shock Proteins/metabolism*
  • Humans
  • Leukocytes/drug effects*
  • Leukocytes/immunology*
  • Leukocytes/metabolism
  • Mice
  • Proto-Oncogene Proteins c-akt/metabolism
  • Signal Transduction/drug effects
  • Spinal Cord/drug effects
  • Spinal Cord/immunology
  • Spinal Cord/metabolism
  • Spinal Cord/pathology
  • Zebrafish
PubMed
25810397 Full text @ J. Immunol.
Abstract
Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90β. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90β and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes