NPY, NPY receptors, and DPP IV activity are modulated by LPS, TNF-alpha and IFN-gamma in HUVEC.
Since NPY increases endothelial cell (EC) stickiness for leukocytes, we studied the effects of LPS, TNF-alpha and IFN-gamma on its expression and action in HUVEC. Cytokines raised NPY and pro-NPY intracellular content and dipeptidyl peptidase IV (DPP IV) activity. Y1 and Y2 receptors were expressed in basal conditions, and LPS, TNF-alpha and IFN-gamma induced Y5 receptor expression with a concomitant extinction of Y2 receptor expression. NPY induced an intracellular calcium increase mainly mediated by Y2 and Y5 receptors in basal conditions. After stimulation with LPS, TNF-alpha and IFN-gamma, calcium increase was mainly caused by Y5 receptor. The modulation of the NPY system by LPS, TNF-alpha and IFN-gamma, and the NPY-induced calcium signaling suggest a role for NPY during the inflammatory response.
Division d'Hypertension et de Médecine Hopital Nestle Vasculaire, Centre Hospitalier Universitaire Vaudois, 1011, Lausanne, Switzerland
Antonio P
AP
Silva
Claudia
C
Cavadas
Bénédicte
B
Baïsse-Agushi
Olivier
O
Spertini
Hans R
HR
Brunner
Eric
E
Grouzmann
D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014470:Umbilical Cord / Q000378:metabolism
D015815:Cell Adhesion Molecules; D008070:Lipopolysaccharides; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D018819:Dipeptidyl Peptidase 4; D002118:Calcium