Regional Susceptibility to TNF-α Induction of Murine Brain Inflammation via Classical IKK/NF-κB Signalling

Young, Adam M. H.; Campbell, Elaine C.; Lynch, Sarah; Dunn, Malcolm H.; Powis, Simon J.; Suckling, John

doi:10.1371/journal.pone.0039049

Cited by 34 publications

(18 citation statements)

References 33 publications

(43 reference statements)

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“…However, when NF-kB transcription is activated by excessive amounts of TNF-a, it leads to production of excitotoxins, reactive oxygen species, and additional proinflammatory cytokines, which, in turn, leads to apoptosis in the absence of active feedback systems. 33,34 Whether and how any of these pathways are involved in ASD will need to be addressed by future experimental studies in mouse models of ASD and confirmed by correlative clinical studies.…”

Section: Discussionmentioning

confidence: 99%

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Gülöksüz

Abali

Çetin

et al. 2017

Rev. Bras. Psiquiatr.

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Objective: To investigate plasma concentrations of S100B (a calcium-binding protein derived primarily from the glia) and inflammatory cytokines in children with autism and the relationship between S100B and cytokine concentrations. Methods: Plasma levels of S100B, tumor necrosis factor alpha (TNF-a), interferon gamma, interleukin (IL)-1b, IL-4, IL-6, IL-10, and IL-17A were measured in 40 unmedicated children with autism and 35 normally developing healthy children. The severity of autism was assessed using the Childhood Autism Rating Scale (CARS). Results: Concentrations of both S100B and TNF-a were higher in children with autism before and after adjusting for a priori-selected confounders (age, sex, and body mass index). S100B concentrations were higher in children with severe autism compared to children with mild-moderate autism. However, this association remained as a trend after adjusting for confounders. S100B concentrations correlated positively with TNF-a concentrations. Conclusion: Our findings showing an increase in peripheral concentrations of S100B and TNF-a provide limited support to the hypothesis about the roles of altered immune function and S100B in autism spectrum disorder (ASD). Studies of larger numbers of well-characterized individuals with ASD are needed to clarify the potential role of the immune system in the pathophysiology of this disorder.

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Section: Discussionmentioning

confidence: 99%

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Gülöksüz

Abali

Çetin

et al. 2017

Rev. Bras. Psiquiatr.

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“…Canonical NF-κB activation triggers the production of cytokines such as IL1β, IL6(51) and IL12, and is inhibited by RPS6KB1 (S6K1). Knockdown of this inhibition results in enhanced production of inflammatory cytokines(19).…”

Section: Discussionmentioning

confidence: 99%

GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis

Hussman¹,

Beecham

Schmidt

et al. 2016

Genes Immun

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Objective To identify genes and biologically relevant pathways associated with risk to develop multiple sclerosis (MS). Methods The Genome-Wide Association Studies noise-reduction method (GWAS-NR) was applied to MS genotyping data. Regions of association were defined based on significance of linkage disequilibrium (LD) blocks. Candidate genes were cross-referenced based on a review of current literature, with attention to molecular function and directly interacting proteins. Supplementary annotations and pathway enrichment scores were generated using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Results The candidate set of 220 MS susceptibility genes prioritized by GWAS-NR was highly enriched with genes involved in biological pathways related to positive regulation of cell, lymphocyte, and leukocyte activation (p=6.1E-15, 1.2E-14, and 5.0E-14, respectively). Novel gene candidates include key regulators of NF-κB signaling and CD4+ T helper type 1 (Th1) and T helper type 17 (Th17) lineages. Conclusions A large subset of MS candidate genes prioritized by GWAS-NR were found to interact in a tractable pathway regulating the NF-κB-mediated induction and infiltration of pro-inflammatory Th1/Th17 T-cell lineages, and maintenance of immune tolerance by T-regulatory cells. This mechanism provides a biological context that potentially links clinical observations in MS to the underlying genetic landscape that may confer susceptibility.

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“…TNF- α was specifically selected to activate the classical NF- κ B signaling cascade of the innate immune system and to stimulate the nuclear translocation of NF- κ B in primary cortical neurons [ 58 ]. NF- κ B DNA binding activity was significantly increased in the peripheral blood samples of children with autism [ 59 ].…”

Section: Cytokines and Autismmentioning

confidence: 99%

Inflammatory Cytokines: Potential Biomarkers of Immunologic Dysfunction in Autism Spectrum Disorders

Zhong

2015

Mediators of Inflammation

169

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Autism is a disorder of neurobiological origin characterized by problems in communication and social skills and repetitive behavior. After more than six decades of research, the etiology of autism remains unknown, and no biomarkers have been proven to be characteristic of autism. A number of studies have shown that the cytokine levels in the blood, brain, and cerebrospinal fluid (CSF) of autistic subjects differ from that of healthy individuals; for example, a series of studies suggests that interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) are significantly elevated in different tissues in autistic subjects. However, the expression of some cytokines, such as IL-1, IL-2, transforming growth factor-β (TGF-β), and granulocyte-macrophage colony-stimulating factor (GM-CSF), is controversial, and different studies have found various results in different tissues. In this review, we focused on several types of proinflammatory and anti-inflammatory cytokines that might affect different cell signal pathways and play a role in the pathophysiological mechanism of autistic spectrum disorders.

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Regional Susceptibility to TNF-α Induction of Murine Brain Inflammation via Classical IKK/NF-κB Signalling

Cited by 34 publications

References 33 publications

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

Elevated plasma concentrations of S100 calcium-binding protein B and tumor necrosis factor alpha in children with autism spectrum disorders

GWAS analysis implicates NF-κB-mediated induction of inflammatory T cells in multiple sclerosis

Inflammatory Cytokines: Potential Biomarkers of Immunologic Dysfunction in Autism Spectrum Disorders

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