Modulation of chemokine production and expression of adhesion molecules in renal tubular epithelial and endothelial cells by catecholamines.
BACKGROUND
The present study was conducted to investigate whether catecholamines influence the production of chemokines and adhesion molecules in proximal tubular epithelial cells (PTECs) and endothelial cells.


METHODS
PTECs and human umbilical vein endothelial cells (HUVECs) were stimulated with various concentrations of dopamine (DA), adrenaline (AD), or noradrenaline (NA), and the production of interleukin (IL)-8, ENA-78, and Gro-alpha was assessed by ELISA. The influence of catecholamine pretreatment on tumor necrosis factor (TNF)-alpha-mediated production of these chemokines and the expression of adhesion molecules was also tested.


RESULTS
In PTECs, DA inhibited the production of all three chemokines in a dose-dependent fashion. Although inhibition in ENA-78 and Gro-alpha production was also found in HUVECs, IL-8 production was up-regulated in these cells. Increased IL-8 secretion was predominantly observed at the apical site of the cells. In AD or NA stimulated cells, the production of Gro-alpha was increased in PTECs and decreased in HUVECs. Down-regulation in IL-8 production was also observed after AD but not after NA stimulation of both cell types. Interestingly, TNF-alpha-mediated up-regulation in intercellular adhesion molecule 1, vascular cell adhesion molecule (VCAM), and E-selectin was delayed in DA-pretreated HUVECs but not in PTECs. The influence of DA, but not AD or NA, on chemokine production was completely prevented by the addition of N-acetylcysteine.


CONCLUSIONS
This study demonstrates that catecholamines differentially influence chemokine production and indicates that DA may have anti-inflammatory properties because it delays the expression of adhesion molecules and inhibits the production of chemokines in PTECs and endothelial cells under basal and inflammatory conditions.
Kapper
Silke
S
Departments of Nephrology and Anaesthesiology, University of Heidelberg at Mannheim, Mannheim, Germany. kapper.s@web.de.
Beck
Grietje
G
Riedel
Saskia
S
Prem
Katharina
K
Haak
Markus
M
van der Woude
Fokko J
FJ
Yard
Benito A
BA
D002395:Catecholamines / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D002395:Catecholamines; D015815:Cell Adhesion Molecules; D018925:Chemokines; D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D004298:Dopamine