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


CONCLUSIONS
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.
Molet
S
S
Montreal General Hospital and the Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada.
Furukawa
K
K
Maghazechi
A
A
Hamid
Q
Q
Giaid
A
A
D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology; D018946:Chemokine CCL5 / Q000502:physiology; D054360:Chemokine CXCL1; D018925:Chemokines / Q000502:physiology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000502:physiology; D016207:Cytokines / Q000502:physiology*; D019332:Endothelin-1 / Q000096:biosynthesis*; D000072396:Endothelin-Converting Enzymes; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D004790:Enzyme Induction / Q000276:immunology; D006133:Growth Substances / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007371:Interferon-gamma / Q000502:physiology; D016209:Interleukin-8 / Q000502:physiology; D008666:Metalloendopeptidases; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology
C475829:CXCL1 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016207:Cytokines; D019332:Endothelin-1; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes