Role of Glycosylation in TOLL-like Receptor Activation and Pro-infl ammatory Responses

2016 ◽  
pp. 175-194
Keyword(s):  
Receptor Activation ◽  
Toll Like Receptor

scholarly journals NFκB1 is essential to prevent the development of multiorgan autoimmunity by limiting IL-6 production in follicular B cells

2016 ◽  
Vol 213 (4) ◽  
pp. 621-641 ◽  
Author(s):  
Elisha de Valle ◽  
George Grigoriadis ◽  
Lorraine A. O’Reilly ◽  
Simon N. Willis ◽  
Mhairi J. Maxwell ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Receptor Activation ◽  
Spontaneous Generation ◽  
B Cell Differentiation ◽  
Toll Like Receptor ◽  
Intrinsic Loss ◽  
And Function ◽  
Follicular B Cells

We examined the role of NFκB1 in the homeostasis and function of peripheral follicular (Fo) B cells. Aging mice lacking NFκB1 (Nfκb1−/−) develop lymphoproliferative and multiorgan autoimmune disease attributed in large part to the deregulated activity of Nfκb1−/− Fo B cells that produce excessive levels of the proinflammatory cytokine interleukin 6 (IL-6). Despite enhanced germinal center (GC) B cell differentiation, the formation of GC structures was severely disrupted in the Nfκb1−/− mice. Bone marrow chimeric mice revealed that the Fo B cell–intrinsic loss of NFκB1 led to the spontaneous generation of GC B cells. This was primarily the result of an increase in IL-6 levels, which promotes the differentiation of Fo helper CD4+ T cells and acts in an autocrine manner to reduce antigen receptor and toll-like receptor activation thresholds in a population of proliferating IgM+ Nfκb1−/− Fo B cells. We demonstrate that p50-NFκB1 represses Il-6 transcription in Fo B cells, with the loss of NFκB1 also resulting in the uncontrolled RELA-driven transcription of Il-6. Collectively, our findings identify a previously unrecognized role for NFκB1 in preventing multiorgan autoimmunity through its negative regulation of Il-6 gene expression in Fo B cells.

scholarly journals Role of scavenger receptors as damage-associated molecular pattern receptors in Toll-like receptor activation

2017 ◽  
Vol 29 (2) ◽  
pp. 59-70 ◽  
Author(s):  
Kyoko Komai ◽  
Takashi Shichita ◽  
Minako Ito ◽  
Mitsuhiro Kanamori ◽  
Shunsuke Chikuma ◽  
...  
Keyword(s):  
Receptor Activation ◽  
Scavenger Receptors ◽  
Toll Like Receptor ◽  
Molecular Pattern

scholarly journals Pathophysiological Cascade of Events Leading to Epilepsy: Role of Inflammation

2021 ◽  
pp. 74-84
Author(s):  
Hadeel Zakaria Alsaegh ◽  
Hala Salah Abd El-Kawy Eweis ◽  
Fatemah Omar Kamel
Keyword(s):  
Acute Phase Proteins ◽  
Epigenetic Modification ◽  
Receptor Activation ◽  
Brain Inflammation ◽  
Seizure Threshold ◽  
Toll Like Receptor ◽  
Necrosis Factor Alpha ◽  
Inflammatory Reactions ◽  
Exact Function

Epileptogenesis is an alteration modification of the typical brain structure, yielding a brain drained by recurring seizures. Such a process is usually precipitated by neurodegeneration, disruption of blood-brain barrier (BBB), the amygdala, the glutamatergic system, oxidative stress, and epigenetic modification deoxyribonucleic acid (DNA). Since there is no efficient method yet, to modify or control this disorder's pathway due to its unclear pathology, novel therapeutic approaches are needed. The risk to develop epilepsy, aggravate the frequency of seizures have been strongly linked to peripheral inflammatory disorders in humans as well as animal studies, with the latter demonstrating a specific association between peripheral inflammatory bowel disorders and peripheral injection of the Toll‐like receptor 4 (TLR4) ligand lipopolysaccharide (LPS) and the increased seizer's frequency and their induced injuries. Understanding the exact function and role of the chemical mediators and receptors involved in the neuroinflammatory reaction could help elucidate their contribution to the pathogenesis of epilepsy. These inflammatory markers include interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α), which are expressed in activated microglia and astrocytes; they trigger the complement system, nuclear factor-kappa b (NF-κB), cyclooxygenase-2 (COX-2), chemokines, and acute-phase proteins. The neural tissues and the endothelial layer of the BBB neurons are involved in these inflammatory reactions. The high-mobility-group Box 1 (HMGB1) fast release from microglia, neurons, and astrocytes after exposure to pro-convulsant insult and Toll-like receptor activation (TLR) signaling in astrocytes and neurons has been proven to be significantly involved in triggering brain inflammation and reducing the seizure threshold. The current review aims to determine the effect of anti-inflammatory drugs on the epilepsy foci rather than treating the symptoms. Such understanding could be the basis of developing a new treatment that could be effective for cases refractory to the current treatment.

Role of Toll-like receptor 1, 2 and 4 on thromboxane B2 production by different microbial products

2018 ◽  
Vol 56 (08) ◽  
pp. e254-e255
Author(s):  
J Zhang ◽  
A Wieser ◽  
H Li ◽  
I Liß ◽  
AL Gerbes ◽  
...  
Keyword(s):  
Thromboxane B2 ◽  
Toll Like Receptor ◽  
Microbial Products

scholarly journals Differential Effects of Toll-Like Receptor Activation and Differential Mediation by MAP Kinases of Immune Responses in Microglial Cells

2021 ◽  
Author(s):  
Jaedeok Kwon ◽  
Christos Arsenis ◽  
Maria Suessmilch ◽  
Alison McColl ◽  
Jonathan Cavanagh ◽  
...  
Keyword(s):  
Map Kinase ◽  
Microglial Activation ◽  
Map Kinases ◽  
Mrna Level ◽  
Cell Types ◽  
Receptor Activation ◽  
Microglial Cells ◽  
Toll Like Receptor ◽  
Disease States ◽  
Nitrite Production

AbstractMicroglial activation is believed to play a role in many psychiatric and neurodegenerative diseases. Based largely on evidence from other cell types, it is widely thought that MAP kinase (ERK, JNK and p38) signalling pathways contribute strongly to microglial activation following immune stimuli acting on toll-like receptor (TLR) 3 or TLR4. We report here that exposure of SimA9 mouse microglial cell line to immune mimetics stimulating TLR4 (lipopolysaccharide—LPS) or TLR7/8 (resiquimod/R848), results in marked MAP kinase activation, followed by induction of nitric oxide synthase, and various cytokines/chemokines. However, in contrast to TLR4 or TLR7/8 stimulation, very few effects of TLR3 stimulation by poly-inosine/cytidine (polyI:C) were detected. Induction of chemokines/cytokines at the mRNA level by LPS and resiquimod were, in general, only marginally affected by MAP kinase inhibition, and expression of TNF, Ccl2 and Ccl5 mRNAs, along with nitrite production, were enhanced by p38 inhibition in a stimulus-specific manner. Selective JNK inhibition enhanced Ccl2 and Ccl5 release. Many distinct responses to stimulation of TLR4 and TLR7 were observed, with JNK mediating TNF protein induction by the latter but not the former, and suppressing Ccl5 release by the former but not the latter. These data reveal complex modulation by MAP kinases of microglial responses to immune challenge, including a dampening of some responses. They demonstrate that abnormal levels of JNK or p38 signalling in microglial cells will perturb their profile of cytokine and chemokine release, potentially contributing to abnormal inflammatory patterns in CNS disease states.

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