Reciprocal control of inflammatory cytokines, IL-1 and IL-6, and β-amyloid production in cultures

Bo, Roberto Del; Angeretti, Nadia; Lucca, Elisa; Simoni, Maria Grazia De; Forloni, Gianluigi

doi:10.1016/0304-3940(95)11384-9

Cited by 184 publications

(44 citation statements)

References 24 publications

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“…Local upregulation of several cytokines, such as interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-·) and transforming growth factorbeta (TGF-ß), was found in AD brains [1]. It has also been shown that inflammatory cytokines, such as IL-1ß, IL-6 or TNF-·, can augment amyloid precursor protein expression [2,3]. In turn, ß-amyloid stimulates proinflammatory cytokine release from monocytes and microglia [4].…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone Inhibits TNF-α Synthesis More Effectively in Alzheimer’s Disease Patients than in Healthy Individuals

Dziedzic

Wybrańska

Dembińska-Kieć

et al. 2003

Dement Geriatr Cogn Disord

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Inflammatory mechanisms are involved in the pathogenesis of Alzheimer’s disease (AD). It is postulated that cytokine synthesis is altered in AD patients compared with nondemented subjects. Glucocorticoids play an important role in cytokine synthesis. We assessed the release of tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10) and interleukin-12 (IL-12) and its regulation by dexamethasone in AD patients in vitro. Cytokine levels were measured using the ELISA method in unstimulated, LPS-stimulated or whole-blood samples incubated with LPS and dexamethasone from 18 AD patients and 12 controls. The cytokine levels spontaneously produced by blood cells after incubation with LPS or LPS and dexamethasone did not differ significantly between groups. Dexamathasone inhibited TNF-α synthesis by LPS-stimulated blood cells more effectively in AD patients than in controls. These results suggest that cytokine synthesis in AD patients could be regulated by glucocorticoids in a different way than in nondemented subjects.

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Section: Introductionmentioning

confidence: 99%

Dexamethasone Inhibits TNF-α Synthesis More Effectively in Alzheimer’s Disease Patients than in Healthy Individuals

Dziedzic

Wybrańska

Dembińska-Kieć

et al. 2003

Dement Geriatr Cogn Disord

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“…The major histopathological hallmarks of AD include amyloid plaques mainly composed of aggregated β-amyloid (Aβ) peptide [12], neurofibrillary tangles (NFTs) consisting of hyper-phosphorylated tau protein [13], and loss of neurons [12]. Aβ has been shown to induce neurotoxicity [14] and to activate microglia, which secrete pro-inflammatory mediators that can also cause neurotoxicity [15]. Notably, the production of Aβ is increased by inflammation [16], indicating the existence of a vicious circle of reciprocal stimulation in AD [15].…”

Section: Introductionmentioning

confidence: 99%

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

et al. 2015

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Inflammation in the brain is a prominent feature in Alzheimer’s disease (AD). Recent studies suggest that chronic inflammation can be a consequence of failure to resolve the inflammation. Resolution of inflammation is mediated by a family of lipid mediators (LMs), and the levels of these specialized pro-resolving mediators (SPMs) are reduced in the hippocampus of those with AD. In the present study we combined analysis of LMs in the entorhinal cortex (ENT) from AD patients with in vitro analysis of their direct effects on neurons and microglia. We probed ENT, an area affected early in AD pathogenesis, by liquid chromatography-tandem mass spectrometry (LC-MS-MS), and found that the levels of the SPMs maresin 1 (MaR1), protectin D1 (PD1) and resolvin (Rv) D5, were lower in ENT of AD patients as compared to age-matched controls, while levels of the pro-inflammatory prostaglandin D2 (PGD2) were higher in AD. In vitro studies showed that lipoxin A4 (LXA4), MaR1, RvD1 and protectin DX (PDX) exerted neuroprotective activity, and that MaR1 and RvD1 down-regulated Aβ42-induced inflammation in human microglia. MaR1 exerted a stimulatory effect on microglial uptake of Aβ42. Our findings give further evidence for a disturbance of the resolution pathway in AD, and indicate that stimulating this pathway is a promising treatment strategy for AD.

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“…It is possible that the elevation of cholesterol and its metabolites may be inducing glial activation and the production of apoE and inflammatory cytokines. The induced glial activation and production of inflammatory cytokines may be involved in the observed amyloid plaque deposition in these animal models since certain inflammatory cytokines are known to enhance APP expression [97][98][99][100][101] and Aβ processing [102,120]. In these animal models, cholesterol appears to have the potential to enhance inflammation, Aβ production, and Aβ deposition with induced apoE expression likely being a contributing component.…”

Section: The Cholesterol-apoe Connection To Glial Inflammationmentioning

confidence: 91%

“…Aβ can induce MCP-1 [94] and MCP-1, in turn, can induce IL-1β and IL-6 [95] as well as superoxide anion production from microglia [96]. IL-1 [97,98], TNF-α [99] and IL-6 [100,101] can further elevate APP expression and processing into Aβ fragments [102], adding to the Aβ burden in a positive feedback loop.…”

Section: Cytokine Cyclementioning

confidence: 99%

Brain Inflammation, Cholesterol, and Glutamate as Interconnected Participants in the Pathology of Alzheimers Disease

Ringheim¹,

Am²

2006

CPD

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Alzheimer's disease (AD) represents one of the most common ailments afflicting the rapidly growing elderly segment of today's population. Despite the vast amount of effort expended in developing a cure, currently approved drugs address only cognitive symptoms that, although important for improving a patient's daily living standard, do not provide a significant delay or halt to disease progression. Early reports that individuals taking anti-inflammatory medications reduce their risk of developing AD has led to the "inflammation hypothesis" of AD and the subsequent testing of these drugs in the clinic. Tests of a select few of these medications in AD clinical trials have, however, yielded disappointing results. Reports of statin-based medications reducing the risk of AD have also led to the testing of this class of drugs in the clinic. Recently, the approval of the NMDA receptor antagonist memantine (Namenda) has provided clinical support for glutamatergic processes in the disease and generated a renewed interest in the role of excitatory amino acids in the etiology of AD. In this review, we take a closer look at these three compelling areas for addressing AD therapeutics: inflammation, cholesterol, and glutamate. We present arguments that these components are interconnected and mutually regulate processes involved in AD progression. Special focus is given to inflammation as a central feature of AD that may be acting in synergy with cholesterol and glutamate to mediate the observed pathophysiology.

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Reciprocal control of inflammatory cytokines, IL-1 and IL-6, and β-amyloid production in cultures

Cited by 184 publications

References 24 publications

Dexamethasone Inhibits TNF-α Synthesis More Effectively in Alzheimer’s Disease Patients than in Healthy Individuals

Dexamethasone Inhibits TNF-α Synthesis More Effectively in Alzheimer’s Disease Patients than in Healthy Individuals

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

Brain Inflammation, Cholesterol, and Glutamate as Interconnected Participants in the Pathology of Alzheimers Disease

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