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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:105

Article

Molet, S ; Furukawa, K ; Maghazechi, A ; Hamid, Q ; Giaid, A

关键词: endothelin;    endothelin-converting enzyme 1;    endothelial cells;    Northern blot;    messenger RNA;    chemokines;    cytokines;    radioimmunoassay;    human;   

DOI  :  10.1016/S0091-6749(00)90084-8

来源: Elsevier

【 摘 要 】

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 alpha-chemokines (IL-8 and melanoma growth-stimulating activator), beta-chemokines (monocyte chemotactic protein 1, macrophage inflammatory protein 1 alpha [MIP-1 alpha], MIP-1 beta, and RANTES), and proinflammatory cytokines (IL-1 beta, TNF-alpha, and IFN-gamma) 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 TNP-alpha, IL-1 beta, and IFN-gamma for 6 and 24 hours. Results: Incubation with the alpha-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 < .05), MTP-1 alpha and RANTES exerted a moderate, but significant, increase on the ET system (P < .05). The cytomix resulted in a significant increase in ET-1 and ECE-1 mRNA expression (P < .05). 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.

【 授权许可】

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