The deleterious effect of high concentrations of D-glucose requires pro-inflammatory preconditioning.
OBJECTIVE
The present study investigated whether high concentrations of D-glucose can trigger pro-inflammatory mechanisms in human aortic smooth muscle cells.


METHODS
The expression and/or the activity of inducible nitric oxide synthase (iNOS), the extracellular signal-regulated kinase (ERK) 1/2 and nuclear factor (NF)-kappaB were studied in cultured human aortic smooth muscle cells (HASMC) in response to increasing concentrations of D-glucose and/or the inflammatory cytokine interleukin (IL)-1beta.


RESULTS
Increasing D-glucose in the medium from 5.5 to 22 mmol/l had no effect on any of these parameters. However, the high concentration of D-glucose did increase iNOS expression in response to low concentrations of IL-1beta (2.5 and 5 ng/ml), as well as the IL-1beta-induced activation of both ERK 1/2 and NF-kappaB. D-glucose also enhanced, concentration-dependently, the expression and activity of iNOS induced by co-incubation with IL-1beta (10 ng/ml). Pretreatment with IL-1beta sensitized the cells to the subsequent effects of high D-glucose.


CONCLUSIONS
The results indicate that high concentrations of D-glucose exacerbate the pro-inflammatory effects of IL-1beta. We suggest that the observed association between inflammation and diabetes is the result of elevated D-glucose enhancing a pre-existing inflammatory condition, rather than a direct effect of D-glucose on the production of inflammatory mediators.
Lafuente
Nuria
N
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Matesanz
Nuria
N
Azcutia
Verónica
V
Romacho
Tania
T
Nevado
Julián
J
Rodríguez-Mañas
Leocadio
L
Moncada
Salvador
S
Peiró
Concepción
C
Sánchez-Ferrer
Carlos F
CF
D001011:Aorta; D002478:Cells, Cultured; D015870:Gene Expression; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000276:immunology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D010770:Phosphotransferases / Q000096:biosynthesis*
D053583:Interleukin-1beta; D016328:NF-kappa B; D019001:Nitric Oxide Synthase; D010770:Phosphotransferases; D005947:Glucose