Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis

Iosif, Robert E.; Ekdahl, Christine T.; Ahlenius, Henrik; Pronk, Cornelis Jan; Bonde, Sara; Kokaia, Zaal; Jacobsen, Sten Eirik W.; Lindvall, Olle

doi:10.1523/jneurosci.2723-06.2006

Cited by 419 publications

(310 citation statements)

References 54 publications

(79 reference statements)

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“…However, several studies have shown that even this classical proinflammatory cytokine can have protective roles in tissue repair and regeneration. In the central nervous system, TNF␣ has been shown to induce proliferation of neural stem cells, likely via interactions with TNFR2 (48,64,65). Treatment with anti-TNF␣ has been linked to the development of demyelinating disease, which may relate to TNF␣'s roles in repair and neurogenesis (66 -68).…”

Section: Discussionmentioning

confidence: 99%

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

Bloom

Metz

Nalawade

et al. 2016

Journal of Biological Chemistry

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Edited by Dennis VoelkerMacrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been implicated in a broad range of inflammatory and oncologic diseases. MIF is unique among cytokines in terms of its release profile and inflammatory role, notably as an endogenous counter-regulator of the anti-inflammatory effects of glucocorticoids. In addition, it exhibits a catalytic tautomerase activity amenable to the design of high affinity small molecule inhibitors. Although several classes of these compounds have been identified, biologic characterization of these molecules remains a topic of active investigation. In this study, we used in vitro LPS-driven assays to characterize representative molecules from several classes of MIF inhibitors. We determined that MIF inhibitors exhibit distinct profiles of anti-inflammatory activity, especially with regard to TNF␣. We further investigated a molecule with relatively low anti-inflammatory activity, compound T-614 (also known as the anti-rheumatic drug iguratimod), and found that, in addition to exhibiting selective MIF inhibition in vitro and in vivo, iguratimod also has additive effects with glucocorticoids. Furthermore, we found that iguratimod synergizes with glucocorticoids in attenuating experimental autoimmune encephalitis, a model of multiple sclerosis. Our work identifies iguratimod as a valuable new candidate for drug repurposing to MIF-relevant diseases, including multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

Bloom

Metz

Nalawade

et al. 2016

Journal of Biological Chemistry

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“…On the other hand, TNFR-2 has been reported to have a positive impact on the neurogenesis process. IL-1B level is correlated with brain neurogenesis including the hippocampal site [69]- [75]. Elevation in levels of IL-6, IL-7, IL-8, IL-10, IFN-α and G-CSF have been demonstrated in recent evidences [28].…”

Section: Cytokines In Depressionmentioning

confidence: 98%

The Role of Immune System in Depression Disorder

Hoseinzadeh¹,

Abadi²,

Agheltar³

et al. 2016

Health

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In order to diagnose a major depressive disorder, patients must have at least 5 depressive symptoms out of 9 criteria, present for at least two weeks. Depressive symptoms include absence of concentration, fatigue and suicidal ideation. The intensity of depression symptoms affects the severity of depression and the degree of the impact on the quality of life. Major depressive disorders (MDD) are defined as a significant health problem, and are estimated to rise in prevalence in the future years. Immune cytokine, associated with major depression for instance, is the interleukin IL-6 and tumor necrosis factor (TNF-α) which is defined as pro-inflammatory cytokines, can activate an inflammatory response. The effects of other inflammatory cytokines on the central nervous system are of controversy. There is an increasing interest about the effect of cytokines derived from innate immune system on the brain and behavior. Cytokines are defined as large sized proteins, mainly produced by immune cells. Two subtypes of cytokines exist: pro-inflammatory cytokines, facilitating inflammatory responses and neural activities; and anti-inflammatory cytokines, inhibiting inflammatory processes. Besides microglia and astrocytes, immune cells such as monocytes, macrophages, and lymphocytes also produce cytokines. At the times of immunological alterations, infections or inflammation, cytokines will be in an activated form. The main goal of the current review study is to investigate the role of the immune system in the depression disorder.

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“…IGF-1 is a known anti-apoptotic factor and recent reports suggest that it plays an important role in promotion of proliferation and diVerentiation of neuronal progenitors [65,107,145]. Contrary to IGF-1, the studies performed on the transgenic animals lacking TNFR1 revealed that TNFR1 acts as a negative regulator of neuronal progenitors in hippocampus and in SVZ area after stroke [59,60].…”

Section: How Brain Inxammatory Response To Ischemic Injury May Avect mentioning

confidence: 99%

Inflammation, plasticity and real-time imaging after cerebral ischemia

2009

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With an incidence of approximately 350 in 100,000, stroke is the third leading cause of death and a major cause of disability in industrialized countries. At present, although progress has been made in understanding the molecular pathways that lead to ischemic cell death, the current clinical treatments remain poorly eVective. There is mounting evidence that inXammation plays an important role in cerebral ischemia. Experimentally and clinically, brain response to ischemic injury is associated with an acute and prolonged inXammatory process characterized by the activation of resident glial cells, production of inXammatory cytokines as well as leukocyte and monocyte inWltration in the brain, events that may contribute to ischemic brain injury and aVect brain recovery and plasticity. However, whether the post-ischemic inXammatory response is deleterious or beneWcial to brain recovery is presently a matter of debate and controversies. Here, we summarize the current knowledge on the molecular mechanisms underlying post-ischemic neuronal plasticity and the potential role of inXammation in regenerative processes and functional recovery after stroke. Furthermore, because of the dynamic nature of the brain inXammatory response, we highlight the importance of the development of novel experimental approaches such as real-time imaging. Finally, we discuss the novel transgenic reporter mice models that have allowed us to visualize and to analyze the processes such as neuroinXammation and neuronal repair from the ischemic brains of live animals.

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Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis

Cited by 419 publications

References 54 publications

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

Identification of Iguratimod as an Inhibitor of Macrophage Migration Inhibitory Factor (MIF) with Steroid-sparing Potential

The Role of Immune System in Depression Disorder

Inflammation, plasticity and real-time imaging after cerebral ischemia

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