Complementary roles of tumor necrosis factor alpha and interferon gamma in inducible microglial nitric oxide generation

Mir, Margalida; Tolosa, Laia; Asensio, Víctor J.; Lladó, Jerònia; Olmos, Gabriel

doi:10.1016/j.jneuroim.2008.07.002

Cited by 46 publications

(42 citation statements)

References 57 publications

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“…4). These results are in line with the idea that iNOS induction is fully attained only when NF-B and STAT-1 cell signalling pathways are simultaneously activated (Mir et al, 2008).…”

Section: Comparison Of Cytokine and No Productionsupporting

confidence: 89%

A new method to isolate microglia from adult mice and culture them for an extended period of time

Moussaud

Draheim

2010

Journal of Neuroscience Methods

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“…4). These results are in line with the idea that iNOS induction is fully attained only when NF-B and STAT-1 cell signalling pathways are simultaneously activated (Mir et al, 2008).…”

Section: Comparison Of Cytokine and No Productionsupporting

confidence: 89%

A new method to isolate microglia from adult mice and culture them for an extended period of time

Moussaud

Draheim

2010

Journal of Neuroscience Methods

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“…The different inflammatory stimuli that activate microglia during neuroinflammation trigger different signaling pathways including p38 MAPK, JNK, NF- κ B, and ERK1/2 [43–46], making it difficult to determine which of them is in fact implicated in the induction of TNF- α expression. In our laboratory, we demonstrated that the sole inhibition of the mitogen-activated protein kinase and ERK kinase (MEK)/ERK signaling pathway with U0126 or apigenin was enough to inhibit the LPS or the IFN- γ -stimulated TNF- α expression in the BV-2 microglial cell line [47]. Similar results had been previously published in human monocytes [48].…”

Section: Tnf-α and Neuroinflammationsupporting

confidence: 53%

“…In this regard, we have demonstrated that IFN- γ and TNF- α have complementary roles in inducible microglial nitric oxide generation [47] and that both cytokines, through the induction of the expression of several prooxidative enzymes, cooperatively induce oxidative stress and motoneuron death [66]. …”

Section: Tnf-α and Neuroinflammationmentioning

confidence: 99%

Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity

Olmos

Lladó

2014

Mediators of Inflammation

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Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine that exerts both homeostatic and pathophysiological roles in the central nervous system. In pathological conditions, microglia release large amounts of TNF-α; this de novo production of TNF-α is an important component of the so-called neuroinflammatory response that is associated with several neurological disorders. In addition, TNF-α can potentiate glutamate-mediated cytotoxicity by two complementary mechanisms: indirectly, by inhibiting glutamate transport on astrocytes, and directly, by rapidly triggering the surface expression of Ca+2 permeable-AMPA receptors and NMDA receptors, while decreasing inhibitory GABAA receptors on neurons. Thus, the net effect of TNF-α is to alter the balance of excitation and inhibition resulting in a higher synaptic excitatory/inhibitory ratio. This review summarizes the current knowledge of the cellular and molecular mechanisms by which TNF-α links the neuroinflammatory and excitotoxic processes that occur in several neurodegenerative diseases, but with a special emphasis on amyotrophic lateral sclerosis (ALS). As microglial activation and upregulation of TNF-α expression is a common feature of several CNS diseases, as well as chronic opioid exposure and neuropathic pain, modulating TNF-α signaling may represent a valuable target for intervention.

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“…Although activation of the NF-jB pathway has been found to exert a protective effect in neurons [27], many studies indicate that it contributes to the up-regulation of AD-inducing pro-inflammatory and cytotoxic genes during the degenerative process of disease [28][29][30]. Taking into consideration these findings, NF-jB can be considered as potential pharmacological targets for Ab-associated neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Magnesium Lithospermate B Protects Neurons Against Amyloid β (1–42)-Induced Neurotoxicity Through the NF-κB Pathway

et al. 2015

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Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, a Chinese traditional herbal medicine colloquially known as Dan Shen. In this study, we investigated the neuroprotective effect of MLB against oligomeric amyloid β (Aβ) (1-42)-induced neurotoxicity in cultured FVB mouse hippocampal neurons. We found that pretreatment with MLB not only prevents a loss in neuronal cell viability following exposure to Aβ (1-42), but also attenuates Aβ (1-42)-induced release of pro-inflammatory cytokines and neuronal apoptosis in a dose-dependent manner. Mechanistic studies show that MLB counteracts Aβ (1-42)-induced activation of the nuclear factor kappa B (NF-κB) pathway, evidenced by the suppression of NF-κB luciferase reporters, decreased expression of phosphorylated Inhibitor κB α and IκB kinase α, and reduced nuclear translocation of p65 in response to pre-treatment with 50 μg/ml MLB prior to Aβ (1-42) exposure. MLB was able to reverse the increase in phosphorylated c-Jun N-terminal kinase (JNK) levels as well as the decrease in phosphorylated Akt levels that are induced by Aβ (1-42), although this finding did not extend to extracellular signal-regulated kinase or p38 kinases. Furthermore, combining MLB with the JNK inhibitor SP600125 synergistically counteracts the Aβ (1-42)-induced reduction in cell viability and neurite growth, and the neuroprotective effects of MLB could be attenuated by the Akt inhibitor triciribine. In conclusion, these results suggest that MLB can protect against Aβ (1-42)-induced neuronal damage, which is most likely to be mediated by the NK-κB pathway.

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Complementary roles of tumor necrosis factor alpha and interferon gamma in inducible microglial nitric oxide generation

Cited by 46 publications

References 57 publications

A new method to isolate microglia from adult mice and culture them for an extended period of time

A new method to isolate microglia from adult mice and culture them for an extended period of time

Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity

Magnesium Lithospermate B Protects Neurons Against Amyloid β (1–42)-Induced Neurotoxicity Through the NF-κB Pathway

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