Regulation of tumour necrosis factor signalling: live or let die

Brenner, Dirk; Blaser, Heiko; Mak, Tak W.

doi:10.1038/nri3834

Cited by 779 publications

(819 citation statements)

References 183 publications

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“…NF-κB activation participates in critical regulatory pathways that oppose apoptosis (27,50). Epithelial cell-specific deletion of IKK2 or IKKγ impairs NF-κB activity and leads to increased cell apoptosis (51,52).…”

Section: Discussionmentioning

confidence: 99%

“…TNF-α is one of the primary cytokines that participate in diverse inflammatory reactions. Upon binding to its two receptors, TNFR1 and TNFR2, TNF-α induces complex intracellular signaling cascades mediating inflammation and promoting cell survival or death (27). We investigated the role of TNF-α, markedly elevated after olfactory lesioning, during neuroregeneration using TNFR1 −/− , TNFR2 −/− , or double-knockout (DKO) mice.…”

Section: Olfactory Neuroregeneration Is Accompanied By An Acute Inflamentioning

confidence: 99%

“…The proinflammatory cytokine TNF-α plays a central role within a complicated network of cytokines activating the NF-κB and JNK signaling pathways (27). Both NF-κB and JNK signaling play crucial roles in mediating the inflammatory response, and cross-talk between these two signaling pathways is recognized (43,44).…”

Section: Loss Of Rela Decreases Neuronal Differentiation and Increasementioning

confidence: 99%

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Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Chen

Reed

Lane

2017

Proc. Natl. Acad. Sci. U.S.A.

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Adult neural stem cells/progenitor cells residing in the basal layer of the olfactory epithelium are capable of reconstituting the neuroepithelium even after severe damage. The molecular events underlying this regenerative capacity remain elusive. Here we show that the repair of neuroepithelium after lesioning is accompanied by an acute, but self-limited, inflammatory process. Attenuation of inflammatory cell recruitment and cytokine production by dexamethasone impairs proliferation of progenitor horizontal basal cells (HBCs) and subsequent neuronal differentiation. Using TNF-α receptor-deficient mice, we identify TNF-α signaling as an important contributor to this inflammatory and reparative process, mainly through TNF-α receptor 1. HBC-selective genetic ablation of RelA (p65), the transcriptional activator of the NF-κB pathway, retards inflammation and impedes proliferation at the early stages of regeneration and suggests HBCs directly participate in cross-talk between immune response and neurogenesis. Loss of RelA in the regenerating neuroepithelium perturbs the homeostasis between proliferation and apoptosis while enhancing JNK signaling. Together, our results support a model in which acute inflammation after injury initiates important regenerative signals in part through NF-κB-mediated signaling that activates neural stem cells to reconstitute the olfactory epithelium.neuroregeneration | inflammation | olfactory stem cells | NF-κB

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Section: Discussionmentioning

confidence: 99%

Section: Olfactory Neuroregeneration Is Accompanied By An Acute Inflamentioning

confidence: 99%

Section: Loss Of Rela Decreases Neuronal Differentiation and Increasementioning

confidence: 99%

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Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Chen

Reed

Lane

2017

Proc. Natl. Acad. Sci. U.S.A.

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“…22 TNF receptor 1 activation can trigger apoptosis and necroptosis, but the latter is favored in case of caspase deactivation. 24 Meanwhile, the first negative regulator of necroptosis has been described. Protein phosphatase 1b dephosphorylates phosphorylated RIPK3, which thereby loses its ability to activate MLKLmediated membrane rupture.…”

Section: Categories Of Regulated Necrosismentioning

confidence: 99%

Necroinflammation in Kidney Disease

Mulay

Linkermann

Anders

2016

Journal of the American Society of Nephrology

189

185

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The bidirectional causality between kidney injury and inflammation remains an area of unexpected discoveries. The last decade unraveled the molecular mechanisms of sterile inflammation, which established danger signaling via pattern recognition receptors as a new concept of kidney injury-related inflammation. In contrast, renal cell necrosis remained considered a passive process executed either by the complement-related membrane attack complex, exotoxins, or cytotoxic T cells. Accumulating data now suggest that renal cell necrosis is a genetically determined and regulated process involving specific outside-in signaling pathways. These findings support a unifying theory in which kidney injury and inflammation are reciprocally enhanced in an autoamplification loop, referred to here as necroinflammation. This integrated concept is of potential clinical importance because it offers numerous innovative molecular targets for limiting kidney injury by blocking cell death, inflammation, or both. Here, the contribution of necroinflammation to AKI is discussed in thrombotic microangiopathies, necrotizing and crescentic GN, acute tubular necrosis, and infective pyelonephritis or sepsis. Potential new avenues are further discussed for abrogating necroinflammation-related kidney injury, and questions and strategies are listed for further exploration in this evolving field.

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“…When necrosis is induced, activated RIP3 binds to MLKL and subsequently phosphorylates MLKL 21. Phosphorylated MLKL can disturb the intact structure of the plasma membranes as well as the organelle membrane and change its permeability 10, 23, 24. The N‐terminal coil‐coil domain of MLKL possesses series of amino acids with positive charges and enables MLKL to interact with the negative‐charged phospholipids of the plasma membrane as well as the different phosphatidylinositol phosphates within organelle membranes (Figure 3).…”

Section: Death Receptor Pathway Of Necrosismentioning

confidence: 99%

Molecular mechanism and therapy application of necrosis during myocardial injury

Ding

Tariq

et al. 2018

J Cellular Molecular Medi

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Necrosis is an ancient topic which gains new attraction in the research area these years. There is no doubt that some necrosis can be regulated by genetic manipulation other than an accidental cell death resulting from physical or chemical stimuli. Recent advances in the molecular mechanism underlying the programmed necrosis show a fine regulation network which indicates new therapy targets in human diseases. Heart diseases seriously endanger our health and have high fatality rates in the patients. Cell death of cardiac myocytes is believed to be critical in the pathogenesis of heart diseases. Although necrosis is likely to play a more important role in cardiac cell death than apoptosis, apoptosis has been paid much attention in the past 30 years because it used to be considered as the only form of programmed cell death. However, recent findings of programmed necrosis and the related signalling pathways have broadened our horizon in the field of programmed cell death and promote new pharmacological application in the treatment of heart diseases. In this review, we summarize the advanced progress in these signalling pathways and discuss the pathos‐physiological relevance and therapeutic implication of targeting necrosis in heart diseases treatment.

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Regulation of tumour necrosis factor signalling: live or let die

Cited by 779 publications

References 183 publications

Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Acute inflammation regulates neuroregeneration through the NF-κB pathway in olfactory epithelium

Necroinflammation in Kidney Disease

Molecular mechanism and therapy application of necrosis during myocardial injury

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