Chemokine- and cytokine-induced expression of endothelin 1 and endothelin-converting enzyme 1 in endothelial cells

Abstract Background: Endothelin 1 (ET-1) is a product of endothelial and many other cell types that possesses a wide range of actions, including vasoconstriction, bronchoconstriction, and mitogenic activity on smooth muscle cells and fibroblasts. ET-1 release and expression is induced in several disease conditions associated with inflammation and cellular injury. Objective: The purpose of this study is to determine the effects of α-chemokines (IL-8 and melanoma growth-stimulating activator), β-chemokines (monocyte chemotactic protein 1, macrophage inflammatory protein 1α [MIP-1α], MIP-1β, and RANTES), and proinflammatory cytokines (IL-1β, TNF-α, and IFN-γ) on the expression of both ET-1 and endothelin-converting enzyme 1 (ECE-1) by human umbilical vein endothelial cells. Methods: Subconfluent monolayers of human umbilical vein endothelial cells were incubated with each chemokine individually for 24 hours or with a mixture (cytomix) of TNF-α, IL-1β, and IFN-γ for 6 and 24 hours. Results: Incubation with the α-chemokines melanoma growth-stimulating activity and IL-8 did not significantly increase ET-1 and ECE-1 messenger (m)RNA expression and had no effect on ET-1 release. Monocyte chemotactic protein 1 exerted the most potent increase in ET-1 and ECE-1 mRNA and ET-1 release among all chemokines studied ( P P P Conclusion: These data demonstrate that, like cytokines, chemokines can induce endothelial ET-1 and ECE-1 in vitro and suggest a possible role for these inflammatory mediators in the induction of the ET system in inflammatory and vascular diseases. (J Allergy Clin Immunol 2000;105:333-8.)