Magnesium sulphate prevents lipopolysaccharide-induced cell death in an in vitro model of the human placenta

Williamson, Rachel D.; McCarthy, Cathal; Kenny, Louise C.; O’Keeffe, Gerard W.

doi:10.1016/j.preghy.2016.08.237

Cited by 6 publications

(4 citation statements)

References 29 publications

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“…Typically this involves injecting LPS at the site of interest for such diseases. Examples of the use of endotoxin in this way include pre‐eclampsia (Cotechini et al ., ; Faas et al ., ; Faas et al ., ; Lin et al ., ; Liu et al ., ; Rademacher, Gumaa & Scioscia, ; Sakawi et al ., ; Williamson et al ., ; Xue et al ., ), Alzheimer's (Zhan et al ., , ), Parkinson's (Barnum & Tansey, ; Byler et al ., ; Cunningham et al ., ; He et al ., ; Hoban et al ., ; Hritcu & Ciobica, ; Hritcu et al ., ; Liu & Bing, ; Miller et al ., ; Orr, Rowe & Halliday, ; Santiago et al ., ; Tufekci, Genc & Genc, ; Z. Zhang et al ., ), rheumatoid arthritis (Izui, Eisenberg & Dixon, ; Nemeth et al ., ), atherosclerosis (Khedoe et al ., ), multiple sclerosis (di Penta et al ., ; Nguyen et al ., ), Guillain‐Barré syndrome (Prendergast & Moran, ), sepsis (Lewis, Seymour & Rosengart, ; Remick & Ward, ), and stroke (Becker et al ., ; Doll et al ., ; Shim & Wong, ). This far‐from‐exhaustive list illustrates well the generality of this phenomenon.…”

Section: Step 4: Microbes Can Produce and Shed Inflammagens Such As Lmentioning

confidence: 99%

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No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre‐eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially ‘external’ causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress‐induced iron dysregulation, and (ii) its ability to awaken dormant, non‐replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.

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Section: Step 4: Microbes Can Produce and Shed Inflammagens Such As Lmentioning

confidence: 99%

“…As well as its role in inducing inflammatory cytokine production, there is some evidence that LPS, albeit commonly bound to proteins that can sequester it, is itself directly cytotoxic [reviewed by Kell & Pretorius () and Williamson et al . ()].…”

Section: Step 7: Direct Induction Of Cell Death By Lpsmentioning

confidence: 99%

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

Kell

2018

Biological Reviews

108

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“…[Magnesium sulfate (1130–1132) has been used as a treatment for eclampsia and, interestingly, prevents LPS-induced cell death in an in vitro model of the human placenta (1133). ]…”

Section: Prevention Strategiesmentioning

confidence: 99%

A Dormant Microbial Component in the Development of Preeclampsia

Kell

Kenny

2016

Front. Med.

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Preeclampsia (PE) is a complex, multisystem disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused. We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is, in fact, microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, and urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “preeclampsia” that we assessed has, in fact, also been shown to be raised in response to infection. An infectious component to PE fulfills the Bradford Hill criteria for ascribing a disease to an environmental cause and suggests a number of treatments, some of which have, in fact, been shown to be successful. PE was classically referred to as endotoxemia or toxemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the etiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.

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“…In human placental perfusion studies, MgSO 4 reduced IL-1β, TNFα and IL-6 production 20, 21 . MgSO 4 inhibited LPS-induced TNFα mRNA expression in the BeWo trophoblast cell line 35 . In human term placental cells, MgSO 4 inhibited IL-6 and TNFα secretion in response to LPS 19 .…”

Section: Discussionmentioning

confidence: 94%

Magnesium sulfate differentially modulates fetal membrane inflammation in a time‐dependent manner

Cross

Nelson

Potter

et al. 2018

American J Rep Immunol

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Magnesium sulphate prevents lipopolysaccharide-induced cell death in an in vitro model of the human placenta

Cited by 6 publications

References 29 publications

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases

A Dormant Microbial Component in the Development of Preeclampsia

Magnesium sulfate differentially modulates fetal membrane inflammation in a time‐dependent manner

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