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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.
IL-1beta → ERK 1/2: " 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 "
IL-1beta → NF-kappaB: " 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 "
iNOS → IL-1beta: " 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 "
iNOS → ERK 1/2: " 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 "
iNOS → ERK 1/2: " 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 "
iNOS → NF-kappaB: " 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 "
iNOS → IL-1beta: " D-glucose also enhanced, concentration-dependently, the expression and activity of iNOS induced by co-incubation with IL-1beta ( 10 ng/ml ) "