Phytochemical Inhibition of Interleukin-4-Activated Stat6 and Expression of VCAM-1

Cellular functions induced by cytokine interleukin (IL)-4 and IL-4 signaling through signal transducer and activator of transcription (Stat)6 typify a Th2-type immune response. We investigated the inhibitor effect of the NFκB blocker parthenolide in the late-phase, Th2-type immune response. Partheno...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2002-04, Vol.292 (4), p.841-847
Main Authors: Schnyder, Bruno, Schnyder-Candrian, Silvia, Panski, Andreas, Bömmel, Heike, Heim, Markus, Duschl, Albert, Moser, René
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
B-cells
B-Lymphocytes - cytology
B-Lymphocytes - drug effects
B-Lymphocytes - metabolism
Cell Line
DNA - metabolism
Dose-Response Relationship, Drug
endothelium
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Endothelium, Vascular - metabolism
Genes, Reporter - drug effects
histamine
Humans
IL-4
Integrin alpha4beta1
Integrins - biosynthesis
Interleukin-4 - pharmacology
Jak2 protein
Janus Kinase 2
Leukocytes - drug effects
Leukocytes - metabolism
Mice
NF-kappa B - antagonists & inhibitors
parthenolide
Phosphorylation - drug effects
Plant Extracts - pharmacology
Protein Binding - drug effects
Protein-Tyrosine Kinases - metabolism
Proto-Oncogene Proteins
Receptors, Lymphocyte Homing - biosynthesis
sesquiterpene lactone
sesquiterpene lactones
Sesquiterpenes - pharmacology
Signal Transduction - drug effects
Stat6
Stat6 protein
STAT6 Transcription Factor
TNF
Trans-Activators - antagonists & inhibitors
Vascular Cell Adhesion Molecule-1 - biosynthesis
VCAM-1
VCAM-1 protein
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cellular functions induced by cytokine interleukin (IL)-4 and IL-4 signaling through signal transducer and activator of transcription (Stat)6 typify a Th2-type immune response. We investigated the inhibitor effect of the NFκB blocker parthenolide in the late-phase, Th2-type immune response. Parthenolide blocked by 90.6 ± 7.4% the IL-4-induced expression of the endothelial vascular cell adhesion molecule (VCAM)-1, a hallmark of extravasation of very late antigen-4-positive leukocytes. The noncytotoxic concentrations of 10 μM parthenolide left a section of the IL-4 receptor signal transduction intact. Parthenolide did not interfere with the immediate IL-4-induced phosphorylation of endothelial Stat6 on its tyrosine residue Y641 and with tyrosine phosphorylation of the adapter molecule, Jak2—both processes are obligatory for dimerization and nuclear translocation of Stat6. But parthenolide inhibited the Stat6 DNA-binding activity in IL-4-stimulated endothelial cells and inhibited the IL-4-driven activation of a luciferase reporter gene under the control of Stat6-responsive elements (IC50 5.11 ± 0.67 μM). Together, these data suggest an anti-chronic disease profile for the sesquiterpene lactone parthenolide.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2002.6754