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

J Allergy Clin Immunol. 2000 Feb;105(2 Pt 1):333-8. doi: 10.1016/s0091-6749(00)90084-8.


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 1alpha [MIP-1alpha], MIP-1beta, and RANTES), and proinflammatory cytokines (IL-1beta, 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 TNF-alpha, IL-1beta, 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). MIP-1alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid Endopeptidases / biosynthesis*
  • Cells, Cultured
  • Chemokine CCL2 / physiology
  • Chemokine CCL5 / physiology
  • Chemokine CXCL1
  • Chemokines / physiology*
  • Chemokines, CXC*
  • Chemotactic Factors / physiology
  • Cytokines / physiology*
  • Endothelin-1 / biosynthesis*
  • Endothelin-Converting Enzymes
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism*
  • Enzyme Induction / immunology
  • Growth Substances / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins*
  • Interferon-gamma / physiology
  • Interleukin-8 / physiology
  • Metalloendopeptidases
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / physiology
  • Umbilical Veins / cytology


  • CXCL1 protein, human
  • Chemokine CCL2
  • Chemokine CCL5
  • Chemokine CXCL1
  • Chemokines
  • Chemokines, CXC
  • Chemotactic Factors
  • Cytokines
  • Endothelin-1
  • Growth Substances
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-8
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • ECE1 protein, human
  • Endothelin-Converting Enzymes