Cell Type-Specific Interleukin-1β Signaling in the CNS

Srinivasan, Deepak; Yen, Jui‐Hung; Joseph, Donald J.; Friedman, Wilma J.

doi:10.1523/jneurosci.5712-03.2004

Cited by 168 publications

(139 citation statements)

References 44 publications

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“…Under our experimental conditions, IL-1 alone had no effect on the basal level of P-CREB. This is consistent with the finding of Srinivasan et al [64], who observed that IL-1β activation by CREB is transient, declining towards the basal level by 30 min. In our studies the IL-1 preincubation time was 2 h. Under specific conditions CREB can play a critical role in promoting the survival of various types of cells, including neurons [27,31,45,74,75].…”

Section: Discussionsupporting

confidence: 93%

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

Tong

Balázs

Soi-ampornkul³

et al. 2008

Neurobiology of Aging

196

142

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The expression of IL-1 is elevated in the CNS in diverse neurodegenerative disorders, including Alzheimer's disease. The hypothesis was tested that IL-1β renders neurons vulnerable to degeneration by interfering with BDNF-induced neuroprotection. In trophic support-deprived neurons, IL-1β compromised the PI3-K/Akt pathway-mediated protection by BDNF and suppressed Akt activation. The effect was specific as in addition to Akt, the activation of MAPK/ ERK, but not PLCγ, was decreased. Activation of CREB, a target of these signaling pathways, was severely depressed by IL-1β. As the cytokine did not influence TrkB receptor and PLCγ activation, IL-1β might have interfered with BDNF signaling at the docking step conveying activation to the PI3-K/Akt and Ras/MAPK pathways. Indeed, IL-1β suppressed the activation of the respective scaffolding proteins IRS-1 and Shc; this effect might involve ceramide generation. IL-1-induced interference with BDNF neuroprotection and signal transduction was corrected, in part, by ceramide production inhibitors and mimicked by the cell-permeable C2-ceramide. These results suggest that IL-1β places neurons at risk by interfering with BDNF signaling involving a ceramide-associated mechanism. Keywords IL-1β; BDNF; signal transduction; cortical neuronsInterleukin-1 (IL-1) is a pluripotent proinflammatory cytokine that is a potent activator of host defense responses to infection and injury both in the periphery and the CNS [59]. However, IL-1 can also exacerbate damage in the CNS resulting from acute insults, such as © 2007 Elsevier Inc. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript cerebral ischemia and trauma, and circumstantial evidence is consistent with a similar role in chronic neurological diseases, such as multiple sclerosis, Parkinson's disease and Alzheimer's disease (AD) [48]. Furthermore, recent genetic studies highlighted the relevance of IL-1 in AD pathogenesis, showing that specific polymorphisms in the IL-1 gene cluster are associated with greatly increased risk for AD, especially for the earlier onset of the disease [23,50]. The view that inflammatory processes play an important role in pathogenesis has been supported by epidemiological studies, showing that certain antiinflammatory drugs result in a slower progression of the disease [2,8,43,77] and in transgenic AD models decrease the number of dystrophic neurites, activated microglia and IL-1 expression [35], although such drugs also modulate the production of the a...

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Section: Discussionsupporting

confidence: 93%

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

Tong

Balázs

Soi-ampornkul³

et al. 2008

Neurobiology of Aging

196

142

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“…IL-1 acts on glia via the NFκB pathway to exacerbate local inflammatory responses and affects hypothalamic and cortical neurons by regulating CREB activity via p38 MAPK signalling, thus coordinating adaptive neuronal responses to stress and injury (Srinivasan et al 2004). In Finally, proinflammatory cytokines that are released in the periphery in stroke subjects, like other stressors, are able to activate the final arm of the HPA axis to start a reverberating cycle to even further worsen the outcome of the injury.…”

Section: ; Hankey 2006) Exposure To Various Stressors Results Inmentioning

confidence: 99%

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Smith

Lawrence

Rodriguez‐Grande

et al. 2013

J Neuroimmune Pharmacol

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Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome.Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infectionsimilar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches.

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“…Neurons sheathed by the reticulate network of astrocytes respond with large increases in their concentration of intracellular calcium (Nedergaard, 1994). CNS cytokines are released from glia to modulate neuronal function (Srinivasan et al, 2004). Glial TNF-␣ modulates synaptic strength in the brain (Beattie et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

“…Independent of release of cytokines from the peripheral site of injury, inflammatory cytokines are induced in the CNS (Lee et al, 2004;Raghavendra et al, 2004;McMahon et al, 2005). It has become clear that CNS cytokines, in association with activated glia, may influence or modulate neuronal function (Srinivasan et al, 2004). Evidence suggests that glia are intimately involved in the active control of neuronal activity (Araque et al, 1999;Frerking, 2004).…”

Section: Introductionmentioning

confidence: 99%

Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

Guo

Wang²,

Watanabe³

et al. 2007

J. Neurosci.

437

503

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The emerging literature implicates a role for glia/cytokines in persistent pain. However, the mechanisms by which these non-neural elements contribute to CNS activity-dependent plasticity and pain are unclear. Using a trigeminal model of inflammatory hyperalgesia, here we provide evidence that demonstrates a mechanism by which glia interact with neurons, leading to activity-dependent plasticity and hyperalgesia. In response to masseter inflammation, there was an upregulation of glial fibrillary acidic proteins (GFAPs), a marker of astroglia, and interleukin-1␤ (IL-1␤), a prototype proinflammatory cytokine, in the region of the trigeminal nucleus specifically related to the processing of deep orofacial input. The activated astroglia exhibited hypertrophy and an increased level of connexin 43, an astroglial gap junction protein. The upregulated IL-1␤ was selectively localized to astrocytes but not to microglia and neurons. Local anesthesia of the masseter nerve prevented the increase in GFAP and IL-1␤ after inflammation, and substance P, a prototype neurotransmitter of primary afferents, induced similar increases in GFAP and IL-1␤, which was blocked by a nitric oxide synthase inhibitor

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Cell Type-Specific Interleukin-1β Signaling in the CNS

Abstract: Interleukin-1␤ (IL-1␤) is a potent and pleiotropic inflammatory cytokine that is highly produced in the CNS

Cited by 168 publications

References 44 publications

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

Interleukin-1β impairs brain derived neurotrophic factor-induced signal transduction

The Immune System in Stroke: Clinical Challenges and Their Translation to Experimental Research

Glial–Cytokine–Neuronal Interactions Underlying the Mechanisms of Persistent Pain

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