Tumor Necrosis Factor α But Not Interleukin 1β Mediates Neuroprotection in Response to Acute Nitric Oxide Excitotoxicity

Turrin, Nicolas P.; Rivest, Serge

doi:10.1523/jneurosci.4032-05.2006

Cited by 123 publications

(95 citation statements)

References 30 publications

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“…3 In this regard, microglia inhibition causes extensive damages in acute models of neurotoxicity, where TNF-a/IL-1b double knockouts have larger nitric oxide-induced neuronal damages compared to their wild-type counterparts. 94 Since microglial cells in these animals are unable to mount a proper innate immune response in this model of neurotoxicity, we propose that microglia are indeed beneficial to the prevention of neuronal death and the re-establishment of a functional neural environment. In addition, a few studies have demonstrated that an immune response in the CNS may be beneficial to the organism since it reduces the amount of amyloid deposition.…”

Section: Innate Immunity and Alzheimer's Diseasementioning

confidence: 89%

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

2006

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The role of innate immunity and microglia in the brain is currently a matter of great debate and controversy. While several studies have provided evidence that they contribute to neurodegeneration in various animal models of brain diseases and traumas, others have shown that their inhibition may in contrast be associated with more damages or less repair. We have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that derive from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These newly recruited cells are specifically attracted to the b-amyloid 40/42 isoforms in vivo and they participate in the elimination of these proteins by phagocytosis. This review presents the mechanisms involved in the control of the innate immune response by microglia and the beneficial properties of such a response in brain diseases, such as AD.

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Section: Innate Immunity and Alzheimer's Diseasementioning

confidence: 89%

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

2006

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“…Pups aged 5-7 d (P5-7) were considered neonates (13,16,19,39). IL-1β −/− mice on a B6 background were the generous gift Scott Berceli (University of Florida, Gainesville, FL) and have been described previously (40). Mixed-sex litters were used for all neonatal studies.…”

Section: Methodsmentioning

confidence: 99%

Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18

Wynn

Wilson

Hawiger

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G + myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with sepsis.IL-18 | IL-17 | sepsis | neonate | pathogenesis

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“…C57BL/6 mice deficient in tumor necrosis factor (TNF) and/or interleukin-1␤ (IL-1␤), or expressing green fluorescent protein (GFP) under the control of the chicken ␤-actin promoter, were generated from breeders originally obtained from The Jackson Laboratory. Genotypes were confirmed by PCR as described previously (Turrin and Rivest, 2006). All experiments were performed on males aged 2-3 months in accordance with the guidelines of the Canadian Council on Animal Care.…”

Section: Methodsmentioning

confidence: 99%

Rod-Shaped Monocytes Patrol the Brain Vasculature and Give Rise to Perivascular Macrophages under the Influence of Proinflammatory Cytokines and Angiopoietin-2

Audoy-Rémus¹,

Richard²,

Soulet³

et al. 2008

J. Neurosci.

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The nervous system is constantly infiltrated by blood-derived sentinels known as perivascular macrophages. Their immediate precursors have not yet been identified in situ and the mechanism that governs their recruitment is mostly unknown. Here, we provide evidence that CD68 ϩ GR1 Ϫ monocytes can give rise to perivascular macrophages in mice suffering from endotoxemia. After adhesion to the endothelium, these monocytes start to crawl, adopt a rod-shaped morphology when passing through capillaries, and can manifest the ability to proliferate and form a long cytoplasmic protuberance. They are attracted in greater numbers during endotoxemia by a combination of vasoregulatory molecules, including TNF (tumor necrosis factor), interleukin-1␤, and angiopoietin-2. After a period of several hours, some of them cross the endothelium to expand the population of perivascular macrophages. Depletion of adherent monocytes and perivascular macrophages can be achieved by injection of anti-angiopoietin-2 peptide-Fc fusion protein. This study extends our understanding of the behavior of monocytes at the blood-brain interface and provides a way to block their infiltration into the nervous tissue under inflammatory conditions.

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Tumor Necrosis Factor α But Not Interleukin 1β Mediates Neuroprotection in Response to Acute Nitric Oxide Excitotoxicity

Cited by 123 publications

References 30 publications

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18

Rod-Shaped Monocytes Patrol the Brain Vasculature and Give Rise to Perivascular Macrophages under the Influence of Proinflammatory Cytokines and Angiopoietin-2

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