Suppression of endothelin-1-induced mitogenic responses of human aortic smooth muscle cells by interleukin-1 beta.
J Clin Invest
; 95(6): 2474-82, 1995 Jun.
Article
em En
| MEDLINE
| ID: mdl-7769093
ABSTRACT
When applied to quiescent human aortic smooth muscle cells (AOSMC), endothelin-1 (ET-1) caused significant increases in mitogen-activated protein kinase (MAPK) activity, [3H]thymidine incorporation, and cell proliferation, confirming an activity of ET-1 as a potent mitogen on AOSMC. As an in vitro model to evaluate the significance of the mitogenic activity of ET-1 on smooth muscle cells during atherogenesis, we studied possible modulations of the responsiveness of the cells by treatment with various cytokines (IL-1 beta, IL-8, TNF alpha, and TGF beta). Of the four cytokines tested, we found that the treatment of the cells with IL-1 beta dramatically reduced the responsiveness of the cells to ET-1; IL-1 beta treatment at the concentration of 0.2 ng/ml for 8 h completely abolished the activity of ET-1 to induce the mitogenic responses. IL-1 beta treatment caused no changes in the responses induced by EGF, basic fibroblast growth factor, or PDGF. Studies on ET-1-induced intracellular signaling events in IL-1 beta-treated cells revealed that the failure of ET-1 to induce mitogenic responses was due to an increase in cAMP formation secondary to ET-1-induced activation of prostanoid metabolism. These findings on AOSMC in vitro raise the possibility that, under some inflammatory conditions in vivo, ETs may work as a negative modulator of smooth muscle cell proliferation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
/
Divisão Celular
/
Endotelinas
/
Interleucina-1
/
Proteínas Serina-Treonina Quinases
/
Proteínas Quinases Dependentes de Cálcio-Calmodulina
/
Proteínas Quinases Ativadas por Mitógeno
/
Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
1995
Tipo de documento:
Article