Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysfunctional endothelial cell activation and cytokines are implicated in preterm labor, a condition commonly treated with the tocolytic agent, magnesium sulfate (MgSO(4)). Based on recent findings showing the inflammatory effects of magnesium deficiency, we examined the effect of MgSO(4) on human umbilical vein endothelial cell (HuVEC) inflammatory responses in vitro. HuVECs isolated from term umbilical cords were incubated with MgSO(4) prior to stimulation with lipopolysaccharide (LPS) and then assessed for endothelial cell activation. Endothelial cell supernatants were assayed for inflammatory mediator production (interleukin-8; IL-8), and endothelial cell-associated intercellular adhesion molecule (ICAM-1) expression was determined. In the absence of LPS stimulation, MgSO(4) had no effect on HuVEC responses. Treatment of HuVECs with MgSO(4) prior to LPS stimulation inhibited inflammatory mediator production (p<0.05) and cell adhesion molecule expression (p<0.05) in a dose-dependent manner. Mechanistic studies showed that MgSO(4) reduced NFkappaB nuclear translocation and protected cytoplasmic IkappaBalpha from degradation in LPS-treated HuVECs. In conclusion, MgSO(4) inhibits endothelial cell activation, as measured by levels of IL-8 and ICAM-1 expression, via NFkappaB. Our results support the hypothesis that MgSO(4) treatment may function as an anti-inflammatory agent during preterm labor.
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PMID:Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFkappaB pathway. 1695 1

Phenotypic modulation of endothelium to a dysfunctional state contributes to the pathogenesis of atherosclerosis, partly through the activation of the transcription factor NFkB. Several data indicate that magnesium deficiency caused by prolonged insufficient intake and/or defects in its homeostasis may be a missing link between diverse cardiovascular risk factors and atherosclerosis. Here we report that endothelial cells cultured in low magnesium rapidly activate NFkB, an event which is prevented by exposure to the anti-oxidant trolox. It is well known that NFkB activation correlates with marked alterations of the cytokine network. In the present study, we show that exposure of endothelial cells to low magnesium increases the secretion of RANTES, interleukin 8 and platelet derived growth factor BB, all important players in atherogenesis. Moreover, we describe the increased secretion of matrix metalloprotease-2 and -9 and of their inhibitor TIMP-2. Interestingly, by zymography we show that metalloprotease activity predominated over the inhibitory effect of TIMP-2. These results indicate that low magnesium promotes endothelial dysfunction by inducing pro-inflammatory and pro-atherogenic events.
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PMID:Magnesium deficiency promotes a pro-atherogenic phenotype in cultured human endothelial cells via activation of NFkB. 2060 Aug 65