Similar effects of resistin and high glucose on P-selectin and fractalkine expression and monocyte adhesion in human endothelial cells.
Resistin and high glucose (HG) are concomitantly present at elevated concentration in diabetic's plasma; both are pro-inflammatory agents acting on vascular cells by mechanisms that are not fully understood. We questioned whether resistin and HG affect the expression of major adhesion molecules, P-selectin and fractalkine in human endothelial cells (HEC). The results showed that in HEC (i) resistin increased P-selectin expression; (ii) HG up-regulated Fk expression; (iii) P-selectin and fractalkine were functional increasing monocyte adhesion to activated cells. Co-stimulation with resistin and HG increased P-selectin and fractalkine mRNA and protein and induced monocyte adhesion, generated an increase in NADPH oxidase activity and of the intracellular reactive oxygen species and activated the NF-kB and AP-1 transcription factors at similar values as those of each activator. In conclusion in HEC, resistin and HG induce the up-regulation of P-selectin and fractalkine and the ensuing increased monocyte adhesion by a mechanism involving oxidative stress and NF-kB and AP-1 activation.
Manduteanu
Ileana
I
Institute of Cellular Biology and Pathology Nicolae Simionescu, Bucharest 050568, Romania. ileana.manduteanu@icbp.ro
Pirvulescu
Monica
M
Gan
Ana Maria
AM
Stan
Daniela
D
Simion
Viorel
V
Dragomir
Elena
E
Calin
Manuela
M
Manea
Adrian
A
Simionescu
Maya
M
D001786:Blood Glucose / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000096:biosynthesis* / Q000235:genetics; D003920:Diabetes Mellitus / Q000097:blood / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019007:P-Selectin / Q000096:biosynthesis* / Q000235:genetics; D017382:Reactive Oxygen Species; D052243:Resistin / Q000378:metabolism* / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
D001786:Blood Glucose; D054428:Chemokine CX3CL1; D016328:NF-kappa B; D019007:P-Selectin; D017382:Reactive Oxygen Species; D052243:Resistin; D018808:Transcription Factor AP-1; D019255:NADPH Oxidases; D005947:Glucose