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. 1995 Jun;95(6):2474–2482. doi: 10.1172/JCI117948

Suppression of endothelin-1-induced mitogenic responses of human aortic smooth muscle cells by interleukin-1 beta.

Y Fujitani 1, H Ninomiya 1, T Okada 1, Y Urade 1, T Masaki 1
PMCID: PMC295928  PMID: 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.

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Selected References

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