Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFκB pathway

Rochelson, Burton; Dowling, Oonagh; Schwartz, Nadav; Metz, Christine N.

doi:10.1016/j.jri.2006.06.004

Cited by 96 publications

(70 citation statements)

References 34 publications

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“…Comparable results were obtained from three independent experiments. Important proinflammatory cytokines, such as TNF␣ or IL-1␤, as well as LPS are known to induce IL-8 expression via NFBcontaining transcription factor complexes targeting the IL-8 promoter (25)(26)(27). To our knowledge, this is the first study to demonstrate that PPAR␦ agonists lead to a concentration-dependent phosphorylation and nuclear translocation of p65 in nonstimulated endothelial cells, thereby increasing NFB DNA binding.…”

Section: Discussionmentioning

confidence: 72%

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

Meißner

Hrgović

Doll

et al. 2010

Journal of Biological Chemistry

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It is well known that IL-8 is also regulated by mRNA stability. To provide further evidence for this concept, we performed mRNA stability assays and found that PPAR␦ agonists induce the mRNA stability of IL-8. In addition, we showed that PPAR␦ agonists induce the phosphorylation of ERK1/2 and p38, which are known to be involved in the increase of mRNA stability. The inhibition of these MAPK signaling pathways resulted in a significant suppression of the induced IL-8 expression and the reduced mRNA stability. Therefore, our data provide the first evidence that PPAR␦ induces IL-8 expression in nonstimulated endothelial cells via transcriptional as well as posttranscriptional mechanisms.Peroxisome proliferator-activated receptors (PPARs) 2 are members of the nuclear receptor/ligand-activated transcription factors superfamily and consist of three different subtypes: PPAR␣, PPAR␦, and PPAR␥. The role of these receptors was originally thought to be restricted to lipid and lipoprotein metabolism, glucose homeostasis, and cellular differentiation (1, 2). PPARs are activated by natural ligands, such as eicosanoids and fatty acids. In addition, synthetic antidiabetic thiazolidinediones and lipid-lowering fibrates have been shown to act as activators of PPAR␥ and PPAR␣, respectively (3, 4). To date, PPAR␦, which is expressed in almost all tissues, is the subtype that still remains an interesting target for new pharmaceutical drugs.New evidence suggests that PPAR␦ plays a crucial role in the regulation of differentiation, cell growth, and the metabolism of lipids and glucose (5, 6). With respect to the development of novel drugs, the effects and side effects of PPAR␦ activators are therefore of great importance.In the last few years, knowledge concerning the impact of PPAR␦ in endothelial cell function has increased. showed that the PPAR␦ agonist L-165041 suppresses C-reactive protein-induced IL-6 expression (10). The expression profile of both cytokines during treatment with various PPAR␦ agonist concentrations in the endothelial quiescent status has yet to be analyzed. Nonetheless, these studies showed that PPAR␦ agonists could suppress the inflammatory processes in activated endothelial cells. The impact of PPAR agonists on the normally quiescent endothelium, however, remains to be elucidated. This could be of significant importance due to the possible broad range of applications of PPAR␦ agonists in various diseases, such as chronic inflammation, glucose metabolism, dyslipidemia, obesity, and cancer therapy, to mention only a small number of possible medical applications.During the process of inflammation, proinflammatory cytokines are produced by various cell types. IL-8 is one of these important cytokines. It is secreted at very low levels from noninduced cells, although the secretion is increased rapidly by a * This work was supported by the Wilhelm Sander Stiftung (M. M.).

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Section: Discussionmentioning

confidence: 72%

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

Meißner

Hrgović

Doll

et al. 2010

Journal of Biological Chemistry

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“…[11][12][13][14][15] Magnesium, a known vasodilator with anti-inflammatory effects, has the potential to alter the pathophysiology of pain crises. [16][17][18][19][20] In addition to work exploring the use of magnesium administered orally to prevent pain crises, 21,22 2 previous single-institution studies examining the effects of IV magnesium on acute pain crisis yielded conflicting results: one showed a shortened length of stay (LOS) from a median of 5 days to a median of 3 days compared with previous hospitalizations by the same individuals. Conversely, a randomized trial conducted in Canada with 104 children and an average LOS of more than 5 days found no decrease in length of hospitalization.…”

Section: Introductionmentioning

confidence: 99%

A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children

Brousseau

Scott

Badaki-Makun

et al. 2015

Blood

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• Intravenous magnesium did not shorten length of stay for pain crisis in children with sickle cell anemia.• Collaboration between pediatric emergency medicine and hematology allowed for successful enrollment in a sickle cell acute management trial.Magnesium, a vasodilator, anti-inflammatory, and pain reliever, could alter the pathophysiology of sickle cell pain crises. We hypothesized that intravenous magnesium would shorten length of stay, decrease opioid use, and improve health-related quality of life (HRQL) for pediatric patients hospitalized with sickle cell pain crises. The Magnesium for Children in Crisis (MAGiC) study was a randomized, double-blind, placebo-controlled trial of intravenous magnesium vs normal saline placebo conducted at 8 sites within the Pediatric Emergency Care Applied Research Network (PECARN). Children 4 to 21 years old with hemoglobin SS or Sb 0 thalassemia requiring hospitalization for pain were eligible. Children received 40 mg/kg of magnesium or placebo every 8 hours for up to 6 doses plus standard therapy. The primary outcome was length of stay in hours from the time of first study drug infusion, compared using a Van Elteren test. Secondary outcomes included opioid use and HRQL. Of 208 children enrolled, 204 received the study drug (101 magnesium, 103 placebo). Between-group demographics and prerandomization treatment were similar. The median interquartile range (IQR) length of stay was 56.0 (27.0-109.0) hours for magnesium vs 47.0 (24.0-99.0) hours for placebo (P 5 .24). Magnesium patients received 1.46 mg/kg morphine equivalents vs 1.28 mg/kg for placebo (P 5 .12). Changes in HRQL before discharge and 1 week after discharge were similar (P > .05 for all comparisons). The addition of intravenous magnesium did not shorten length of stay, reduce opioid use, or improve quality of life in children hospitalized for sickle cell pain crisis. This trial was registered at www.

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“…According to our results, since the IL-6 basal level was significantly reduced after supplementation, we might suppose that Mg could be included in the HPA-IL-6 relation and more studies should be conducted to explore this communication. A group of researchers have been on the track of a possible mechanism of magnesium action on cytokine release, as they showed that MgSO 4 attenuates cytokine production by lipopolysaccharide (LPS)-stimulated endo thelial cells and placental explants (27)(28)(29). These research groups proved that treatment of human umbilical vein endothelial cells and human placental explants with MgSO 4 prior to LPS stimulation inhibited inflammatory mediator production by suppressing the activation of the transcription factor, nuclear factor-kappa B (NFkB).…”

Section: Discussionmentioning

confidence: 99%

“…These research groups proved that treatment of human umbilical vein endothelial cells and human placental explants with MgSO 4 prior to LPS stimulation inhibited inflammatory mediator production by suppressing the activation of the transcription factor, nuclear factor-kappa B (NFkB). Some earlier studies showed that in vitro and in vivo Mg sup plementation increased basal IkBa levels and reduced NFkB activation, thereby decreasing production of cytokines and chemokines (27,28,30). Furthermore, it was shown that short-term exposure to a clinically effective MgSO 4 concentration in vitro reduced the frequency of neonatal monocytes producing TNF-a and IL-6, decreasing cytokine gene and protein expression (30).…”

Section: Discussionmentioning

confidence: 99%

Pituitary-Gonadal, Pituitary-Adrenocortical Hormones and IL-6 Levels Following Long-Term Magnesium Supplementation in Male Students

Zogović¹,

Pešić²,

Dmitrašinović³

et al. 2014

Journal of Medical Biochemistry

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SummaryBackground: Sleep deprivation, malnutrition and lack of physical activity are contemporary stress-related factors present in the student population. Stress activates the HPA and often suppresses the HPG axis, but also influences cytokine synthesis and consequently regulates immune response. Since magnesium deficiency facilitates negative pathophysiological consequences, a reasonable question imposes, wheth er Mg supplementation might correct the adrenal/gon adal hormone balance and immuno-endocrine function. Methods: Fifteen male students were given 2 × 250 mg Mg for four weeks. Serum levels of FSH, LH, testosterone (T), ACTH and cortisol (C) were measured before and after supplementation and the T/C ratio was calculated. Furthermore, IL-6, red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC) and the WBC differential were measured. Results: Despite no change in the serum level of ACTH, a statistically significant (p<0.05) decrease in the serum cortisol level appeared, accompanied with an IL-6 level reduction (p<0.05) after Mg supplementation. Analysis of the pituitarygonadal axis hormones showed an increasing trend of the FSH level (p=0.087), and a significant increase (p<0.05) in the T/C ratio. An RBC count increase (p<0.001) was found, along with a decrease in the percentage of neutrophils (p< 0.05), and a trend toward a lymphocyte percentage increase. Conclusions:The results suggest that chronic oral magnesium supplementation in male students improves the balance of pituitary-gonadal and pituitary-adrenal hormones and is involved in the regulation of the basal IL-6 level.

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Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFκB pathway

Cited by 96 publications

References 34 publications

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

Peroxisome Proliferator-activated Receptor δ Activators Induce IL-8 Expression in Nonstimulated Endothelial Cells in a Transcriptional and Posttranscriptional Manner*

A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children

Pituitary-Gonadal, Pituitary-Adrenocortical Hormones and IL-6 Levels Following Long-Term Magnesium Supplementation in Male Students

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