Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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Research Abstract |
INTRODUCTION : Cell-surface E-selectin is a mediator of the rolling attachment of leukocytes to the endothelium, an essential step in extravasation of leukocytes at the site of inflammation, thereby playing a key role in localized inflammatory response. Elevated levels of soluble E-selectin in serum have been reported in a variety of pathological conditions. But there are no reports about the direct effect of anesthetics on soluble E-selectin production. The aim of this study was to examine the effects of anesthetics on soluble E-selectin release and E-selectin expression in cultured human umbilical vein endothelial cells (HUVECs). METHODS : Confluent HUVECs were preincubated with ketamine (0,10,100μM) at 37℃ for 2 h and then the confluent monolayer cells were further incubated for 4 h in the absence or the presence of IL-1 (5U/ml). After incubation, the culture medium was collected, centrifuged to remove cell debris, and used as a condtioned medium (CM). The concentrations of soluble E
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-Selectin in the CM were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). Furthermore, we assessed E-selectin mRNA levels by Northern blottiong. RESULTS : In the absence of ketamine, treatment with IL-1 caused a significant (p<0.05) increase in the level of soluble E-Selectin. In contrast, pretreatment of ketamine significantly reduced the stimulatory effect of IL-1. About 70% of the secretion was inhibited by 10μM ketamine. In the absence of IL-1, ketamine treatment did not cause a significant change in its soluble E-Selectin value. The mRNA encoding E-selectin was expressed much more slowly and to a lesser extent under the presence of ketamine. DISCUSSION : These results suggest that ketamine suppresses the production and release of soluble E-Selectin from IL-1 stimulated HUVECs. at least in part by down-regulation of the E-Selectin mRNA expression. Our study suggests that ketamine could be used in patients with the systemic inflammatory response syndrome through its inhibitory effect on soluble E-Selectin production. Less
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