Role of Microglial-Derived Tumor Necrosis Factor in Mediating CD14 Transcription and Nuclear Factor κ B Activity in the Brain during Endotoxemia

Nadeau, Sylvain; Rivest, Serge

doi:10.1523/jneurosci.20-09-03456.2000

Cited by 185 publications

(143 citation statements)

References 29 publications

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“…Activated microglia and macrophages release inflammatory cytokines, prostaglandins, and nitric oxide, possibly leading to neuronal excitability and neuronal damage (45). In our study, TMEV-infected mice had significantly higher expression of MHC class II and CD86 on monocytes, indicating that microglia and macrophages were highly activated (Fig.…”

Section: Discussionsupporting

confidence: 49%

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Cusick

Libbey

Patel

et al. 2013

J Virol

173

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b Viral infections of the central nervous system (CNS) can trigger an antiviral immune response, which initiates an inflammatory cascade to control viral replication and dissemination. The extent of the proinflammatory response in the CNS and the timing of the release of proinflammatory cytokines can lead to neuronal excitability. Tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6), two proinflammatory cytokines, have been linked to the development of acute seizures in Theiler's murine encephalomyelitis virus-induced encephalitis. It is unclear the extent to which the infiltrating macrophages versus resident CNS cells, such as microglia, contribute to acute seizures, as both cell types produce TNF-␣ and IL-6. In this study, we show that following infection a significantly higher number of microglia produced TNF-␣ than did infiltrating macrophages. In contrast, infiltrating macrophages produced significantly more IL-6. Mice treated with minocycline or wogonin, both of which limit infiltration of immune cells into the CNS and their activation, had significantly fewer macrophages infiltrating the brain, and significantly fewer mice had seizures. Therefore, our studies implicate infiltrating macrophages as an important source of IL-6 that contributes to the development of acute seizures.

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Section: Discussionsupporting

confidence: 49%

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Cusick

Libbey

Patel

et al. 2013

J Virol

173

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“…Bone marrowderived microglia are known to infiltrate regions suffering from demyelination and remyelination 56 and microglia are responsible for the majority of TNF-a production in the brain in response to immune stimuli. 57 Their presence and activation at demyelination sites would thus be beneficial for the CNS in order to promote remyelination. Consequently, inhibiting specific inflammatory pathways may be suitable during demyelinating episodes, but not during remyelination and repair.…”

Section: Bone Marrow-derived Cells and Neurodegenerative Diseasesmentioning

confidence: 99%

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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“…The riboprobes used in this study are described in Table I and in situ hybridization using 35 S-labeled cRNA probes was accomplished as described previously (8).…”

Section: Brain Preparation and In Situ Hybridization Histochemistrymentioning

confidence: 99%

Endotoxemia Prevents the Cerebral Inflammatory Wave Induced by Intraparenchymal Lipopolysaccharide Injection: Role of Glucocorticoids and CD14

Nadeau

Rivest

2002

The Journal of Immunology

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There is a robust and transient innate immune response in the brain during endotoxemia, which is associated with a cascade of NF-κB signaling events and transcriptional activation of genes that encode TNF-α and the LPS receptor CD14. The present study investigated whether circulating LPS has the ability to modulate the cerebral innate immune response caused by an intrastriatal (IS) injection of the endotoxin. We also tested the possibility that CD14 plays a role in these effects and male rats received an intracerebroventricular injection with an anti-CD14 before the IS LPS administration. The single LPS bolus into the striatum caused a strong and time-dependent transcriptional activation of TNF-α, IκBα, CD14, and monocyte chemoattractant protein-1 mRNA in microglial cells ipsilateral to the site of injection. Surprisingly, this wave of induced transcripts was essentially abolished by the systemic endotoxin pretreatment. Such anti-inflammatory properties of circulating LPS are mediated via plasma corticosterone, because exogenous corticoids mimicked while glucocorticoid receptor antagonist RU486 prevented the effects of systemic endotoxin challenge. Of interest is the partial involvement of CD14 in LPS-induced neuroinflammation; the anti-CD14 significantly abolished the microglial activity at day 3, but not at times earlier. The inflammatory response provoked by an acute intraparenchymal LPS bolus was not associated with convincing neurodegenerative processes. These data provide compelling evidence that systemic inflammation, through the increase in circulating glucocorticoids, has the ability to prevent the cerebral innate immune reaction triggered by an IS endotoxin injection. This study also further consolidates the existence of such system in the brain, which is finely regulated and its transient activation is not harmful for the neuronal elements.

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Role of Microglial-Derived Tumor Necrosis Factor in Mediating CD14 Transcription and Nuclear Factor κ B Activity in the Brain during Endotoxemia

Cited by 185 publications

References 29 publications

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

Infiltrating Macrophages Are Key to the Development of Seizures following Virus Infection

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

Endotoxemia Prevents the Cerebral Inflammatory Wave Induced by Intraparenchymal Lipopolysaccharide Injection: Role of Glucocorticoids and CD14

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