| Autor: |
Coulpier, M., Andreev, S., Lemercier, C., Dauchel, H., Lees, O., Fontaine, M., Ripoche, J. |
| Předmět: |
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| Zdroj: |
Clinical & Experimental Immunology; Jul1995, Vol. 101 Issue 1, p142-149, 8p |
| Abstrakt: |
Constitutive secretion of complement C3 and factor B by the endothelial cell (EC) is lowered by therapeutic concentrations of glucocorticoids such as hydrocortisone or dexamcthasone, whereas regulatory protein factor H production is increased by these hormones. In contrast, the proinflammatory cytokine IL-1α has a stimulatory effect on C3 and factor B secretion by the endothelium and an inhibitory effect on factor H secretion. In this study, we examined the combined effect of IL-1α and glucocorticoids on C3 and factor B expression by the endothelial cell. When dexamethasone or hydrocortisone were added to IL-1α, significant potentialization of IL 1α- induced stimulation of C3 and factor B production was observed, occurring at various concentrations of either stimuli. Dose-response experiments indicate that, in vitro, optimal concentrations are in the range of 10-7 to 10-5 M for dexamethasone and 50-200U for IL-1α. In contrast, dexamethasone counteracts, in an additive way, the inhibitory effect of IL-1α on regulatory complement protein factor H production by EC. Such a potentialization between glucocorticoids and IL-1α was not observed for another marker of endothelial activation, IL-1α induced stimulation of coagulation tissue factor expression. The association of glucocorticoids and IL-1α therefore appears to be a specific and major stimulus for the secretion of complement C3 and factor B, two acute-phase proteins, by the endothelium. As a result of the in vitro endothelium stimulation by glucocorticoids and IL-1α, C3a is generated in the vicinity of the endothelial cell. This study further suggests that complement activation, with its deleterious consequences, may result from the stimulation of endothelium in situations where high levels of IL-1α and endogenous glucocorticoids coexist, such as in septic shock. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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