Possible Protecting Role of TNF-&amp;#945; in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NF&amp;#954;B Signaling Pathway

Zhang, Xingmei; Zheng, Xiangyu; Sharkawi, Sara Shaaban; Ruan, Yang; Amir, Naheed; Azimullah, Sheikh; Al‐Hasan, Muath; Zhu, Jie; Adem, Abdu

doi:10.2174/15672050113109990007

Cited by 8 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also found that KA treatment changed the degree of anxiety in the elevated plus maze (Zhang et al 2013b). We have several speculations to clarify the mechanism as regards how KA induces excitotoxic neurodegeneration through intranasal administration.…”

Section: Neurodegenerative Animal Model Induced By Intranasal Adminismentioning

confidence: 73%

“…TNF-α has been proved to mediate the disruption of longterm potentiation and related memory mechanisms produced by amyloid and amyloid oligomers in AD models (Tobinick 2009;Wang et al 2005a). TNF-α also bears neuroprotective properties in contrast to its well-known deleterious role as a proinflammatory cytokine, which implies an intricate biological effect in immune and inflammatory responses mediated by TNF-α (Lu et al 2008;Zhang et al 2013b). For example, TNF-α deficiency worsened Listeria infection (Rothe et al 1993) and the neuronal damage was enhanced after excitotoxicity in mice lacking the TNF-α receptors (Lu et al 2008).…”

Section: Tnf-αmentioning

confidence: 99%

See 1 more Smart Citation

IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response

Zhang¹,

Azimullah²,

Zheng³

et al. 2012

Journal of Neuroimmunology

Self Cite

View full text Add to dashboard Cite

Section: Neurodegenerative Animal Model Induced By Intranasal Adminismentioning

confidence: 73%

Section: Tnf-αmentioning

confidence: 99%

IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response

Zhang¹,

Azimullah²,

Zheng³

et al. 2012

Journal of Neuroimmunology

Self Cite

View full text Add to dashboard Cite

“…Studies have shown that the NF‐κB signal transduction pathway participates in the inflammatory immune response induced by macrophages [39]. NF‐κB activity was closely related to the number, state, degree and product of microglial activation, which means the higher the NF‐κB activity, the more activated microglial cells and the more inflammatory factors [40]. Therefore, we hypothesized that blocking the NF‐κb pathway can reduce the polarization of M1 macrophages, increase the number of M2 macrophages and relieve the symptoms of EAE.…”

Section: Discussionmentioning

confidence: 99%

Adoptive transfer of immunomodulatory M2 macrophages suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice via blockading NF-κB pathway

Chu

Shi

Lang

et al. 2021

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Macrophages play important roles in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), and M2 macrophage may have anti-inflammatory effects. In this study, we elucidated the roles of M1 and M2 macrophages in the pathogenesis of EAE and the effects of treatment with M2 macrophages that target certain proinflammatory cytokines and with immunomodulatory preparations that beneficially influence the disease course. We found macrophages increased at the onset of clinical signs in the EAE group, consistent with an increased proportion of M1 macrophages and low numbers of M2 macrophages. As the disease progressed and the symptoms worsened, M1 macrophages decreased and M2 macrophages gradually increased until the peak. In the recovery stage, M2 macrophages gradually decreased. Treatment with M2 macrophages inhibited the nuclear factor kappa B (NF-κB) pathway, alleviated the symptoms of EAE, reduced inflammatory cell infiltration and demyelination in the central nervous system and decreased the numbers of macrophages in the spleens. BAY-11-7082, an NF-κB blocking agent, could reduce the total number of macrophages both in vivo and in vitro, effectively prevented EAE development and significantly inhibited EAE symptoms in mice. Our study demonstrates that macrophages may play a crucial role in the pathogenesis of EAE, while M2 macrophages have anti-inflammatory effects. Transfer of M2 macrophages to EAE mice can block the NF-κB pathway successfully and relieve EAE symptoms. Application of NF-κB blockers is useful in the prevention and treatment of EAE.

show abstract

“…However, this finding is contrary to our previous study in vivo that TNF-α may play a protective role in KA-induced neurotoxicity via down-regulation of NFκB signaling pathway. 13 Regarding the opposite results, we delineated several potential possibilities. Firstly, the two studies were carried out in different conditions, one in vivo and another in vitro.…”

Section: Figure 5imentioning

confidence: 99%

“…12 Previously, our study revealed that KA insult results in more severe seizures, greater hippocampal neurodegeneration and increased glial activation in TNF-α deficient mice, suggesting that TNF-α may play a protective role in KAinduced neurotoxicity. 13 Since the role of TNF-α in neurodegenerative disorders is controversial, in the present study, we further clarified the role of TNF-α in the excitotoxic neurodegeneration in vitro and elucidated its possible involvement of signalling pathways in TNF-α knockout (KO) mice and C57BL/6 wild-type (WT) mice by using primary neuronal cell cultures. In addition, we studied the effects of exogenous TNF-α and blocking TNF-α molecule by anti-TNF-α antibody on KA insult of neuronal cells from WT mice.…”

Section: Introductionmentioning

confidence: 97%

TNF-Α Protection of Hippocampal Neurons from Kainic Acid Induced Neurodegeneration is Associated with Up-Regulation of Nfκb and AKT as well as Down-Regulation of P38 MAPK Signaling Molecules

Zhu¹

2015

MOJT

Self Cite

View full text Add to dashboard Cite

Background: Previously, our study showed that TNF-α plays a protective role in kainic acid (KA) induced neurodegeneration in vivo in mice. Here, we further clarified the protective role of TNF-α in KA-induced hippocampal neuronal damage in vitro and elucidated the potential signaling pathways. Methods: Hippocampal neurons were isolated from embryonic 16 days (E16) TNF-α knockout (KO) and wild-type (WT) mice with C57BL/6 background, respectively, and exposed to KA with and without recombinant TNF-α, as well as anti-TNF-α antibody. After 24-hours exposure to KA, lactate dehydrogenase (LDH) production and neurotoxicity were detected for evaluating neuronal survival rates. The production of nitric oxide (NO) from supernatants and the expression of nuclear factor kappa B (NFкB), inhibitor of NFкB alpha (IκBα), p38 mitogen-activated protein kinase (MAPK) and AKT in hippocampal neurons were measured. Results: Comparing with WT mice, the neurons of TNF-α KO mice showed more susceptibility to KA-induced neurotoxicity, as demonstrated by higher production of LDH and lower neuronal survival rates, as well as elevated NO production. It is also evidenced that pre-blocked TNF-α molecule in the neuron cultures of WT mice with anti-TNF-α antibody significantly enhanced the production of LDH and NO, and decreased the neuronal survival rate. In contrast, the neurons from WT mice pre-exposed to recombinant TNF-α were more resistant to KA induced neurotoxicity. TNF-α deficiency down-regulated phospho-IκBα, NFкB, total AKT and phospho-AKT, as well as up-regulated phospho-p38 MAPK expressions after KA insult. The reverse results were achieved in WT hippocampal neurons with TNF-α pre-administration. Conclusion: Our findings demonstrated an association between the protective effect of TNF-α on neurons as assessed following KA insult, with the up-regulation of NFκB and AKT, as well as down-regulation of p38 MAPK signaling molecules..

show abstract

Possible Protecting Role of TNF-α in Kainic Acid-induced Neurotoxicity Via Down-Regulation of NFκB Signaling Pathway

Cited by 8 publications

References 0 publications

IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response

IFN-γ deficiency exacerbates experimental autoimmune neuritis in mice despite a mitigated systemic Th1 immune response

Adoptive transfer of immunomodulatory M2 macrophages suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice via blockading NF-κB pathway

TNF-Α Protection of Hippocampal Neurons from Kainic Acid Induced Neurodegeneration is Associated with Up-Regulation of Nfκb and AKT as well as Down-Regulation of P38 MAPK Signaling Molecules

Contact Info

Product

Resources

About