Phytochemical inhibition of interleukin-4-activated Stat6 and expression of VCAM-1.
Biochem Biophys Res Commun
; 292(4): 841-7, 2002 Apr 12.
Article
en En
| MEDLINE
| ID: mdl-11944890
ABSTRACT
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 NFkappaB 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 microM 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 (IC(50) 5.11 +/- 0.67 microM). Together, these data suggest an anti-chronic disease profile for the sesquiterpene lactone parthenolide.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
/
Extractos Vegetales
/
Transactivadores
/
Proteínas Proto-Oncogénicas
/
Interleucina-4
/
Molécula 1 de Adhesión Celular Vascular
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2002
Tipo del documento:
Article
País de afiliación:
Suiza