Interferon-β1a protects neurons against mitochondrial toxicity via modulation of STAT1 signaling: Electrophysiological evidence

Tozzi, Alessandro; Tantucci, Michela; Arcangeli, Sara; Chiasserini, Davide; Ghiglieri, Veronica; Iure, Antonio de; Calabresi, Paolo

doi:10.1016/j.nbd.2013.09.022

Cited by 16 publications

(7 citation statements)

References 39 publications

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“…Methods of boosting IFN-α release may open a new avenue for pain management. Notably, IFN-α may produce neurotoxicity while IFN-β has neuroprotective effects 56 57 . It remains to be investigated if IFN-β, a very close family member of IFN-α (both belong to Type I Interferon), plays the same role in pain regulation.…”

Section: Discussionmentioning

confidence: 99%

Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions

Liu

Gao

Luo

et al. 2016

Sci Rep

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It is well known that interferons (IFNs), such as type-I IFN (IFN-α) and type-II IFN (IFN-γ) are produced by immune cells to elicit antiviral effects. IFNs are also produced by glial cells in the CNS to regulate brain functions. As a proinflammatory cytokine, IFN-γ drives neuropathic pain by inducing microglial activation in the spinal cord. However, little is known about the role of IFN-α in regulating pain sensitivity and synaptic transmission. Strikingly, we found that IFN-α/β receptor (type-I IFN receptor) was expressed by primary afferent terminals in the superficial dorsal horn that co-expressed the neuropeptide CGRP. In the spinal cord IFN-α was primarily expressed by astrocytes. Perfusion of spinal cord slices with IFN-α suppressed excitatory synaptic transmission by reducing the frequency of spontaneous excitatory postsynaptic current (sEPSCs). IFN-α also inhibited nociceptive transmission by reducing capsaicin-induced internalization of NK-1 and phosphorylation of extracellular signal-regulated kinase (ERK) in superficial dorsal horn neurons. Finally, spinal (intrathecal) administration of IFN-α reduced inflammatory pain and increased pain threshold in naïve rats, whereas removal of endogenous IFN-α by a neutralizing antibody induced hyperalgesia. Our findings suggest a new form of neuronal-glial interaction by which IFN-α, produced by astrocytes, inhibits nociceptive transmission in the spinal cord.

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Section: Discussionmentioning

confidence: 99%

Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions

Liu

Gao

Luo

et al. 2016

Sci Rep

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“…In an Alzheimer s mouse model (APP SWE /PS1 DE9 ), deletion of IFNAR1 shifts astrocytes to a more anti-inflammatory phenotype by downregulating pro-inflammatory factors [such as inducible nitric oxide synthases (iNOS), integrin aM (CD11b), and Siglec-3 (CD33)] and the upregulation of anti-inflammatory phenotypic markers (transforming growth factor beta (TGF-ß), chitinase-like protein 3 (YM1), arginase 1 (ARG1), and triggering receptor expressed on myeloid cells 2 (TREM2)) (Minter et al, 2016). It was concluded from initial studies that IFN-b exerts a direct effect on neurons, providing a certain degree of protection against neurotoxic and inflammatory insults (Di Filippo et al, 2014). With the help of electrophysiological recordings from coronal brain slices cut from 4 to 8 week-old C57Bl/6 mice, IFN-b1a was shown to modulate glutamatergic neurotransmission in the striatum, a brain region prone to degenerate during multiple sclerosis (Di Filippo et al, 2016).…”

Section: Type I Ifn Responding Cells In the Cns During Diseasementioning

confidence: 99%

Type I interferon pathway in CNS homeostasis and neurological disorders

Blank

Prinz

2017

Glia

122

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Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS). Furthermore, IFNs can reach the CNS from the periphery to modulate the function of not only microglia and astrocytes, but also neurons and oligodendrocytes, with major consequences for cognition and behavior. Given the pleiotropic nature of type I IFNs, it is critical to determine their exact cellular impact. Inappropriate upregulation of type I IFN signaling and interferon-stimulated gene expression have been linked to several CNS diseases termed "interferonopathies" including Aicardi-Goutieres syndrome and ubiquitin specific peptidase 18 (USP18)-deficiency. In contrast, in the CNS of mice with virus-induced neuroinflammation, type I IFNs can limit production of other cytokines to prevent potential damage associated with chronic cytokine expression. This capacity of type I IFNs could also explain the therapeutic benefits of exogenous type I IFN in chronic CNS autoimmune diseases such as multiple sclerosis. In this review we will highlight the importance of a well-balanced level of type I IFNs for healthy brain physiology, and to what extent dysregulation of this cytokine system can result in brain 'interferonopathies'.

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“…However, there is also evidence for selectivity in the IFN responses controlled by the p38 MAPK, suggesting differential regulation of target genes by p38 signals. For instance, the neuroprotective effect of IFNβ against mitochondrial toxicity occurs via modulation of Stat1 activity, but it seems to be p38 MAPK-independent (65). …”

Section: Map Kinase Pathwaysmentioning

confidence: 99%

Interferon Receptor Signaling in Malignancy: A Network of Cellular Pathways Defining Biological Outcomes

Fish

Platanias

2014

Molecular Cancer Research

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Interferons (IFNs) are cytokines with important anti-proliferative activity and exhibit key roles in immune surveillance against malignancies. Early work initiated over 3 decades ago led to the discovery of IFN receptor activated Jak-Stat pathways and provided important insights into mechanisms for transcriptional activation of interferon stimulated genes (ISGs) that mediate IFN-biological responses. Since then, additional evidence has established critical roles for other receptor activated signaling pathways in the induction of IFN-activities. These include MAPK pathways, mTOR cascades and PKC pathways. In addition, specific microRNAs (miRNAs) appear to play a significant role in the regulation of IFN-signaling responses. This review focuses on the emerging evidence for a model in which IFNs share signaling elements and pathways with growth factors and tumorigenic signals, but engage them in a distinctive manner to mediate anti-proliferative and antiviral responses.

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Interferon-β1a protects neurons against mitochondrial toxicity via modulation of STAT1 signaling: Electrophysiological evidence

Cited by 16 publications

References 39 publications

Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions

Interferon alpha inhibits spinal cord synaptic and nociceptive transmission via neuronal-glial interactions

Type I interferon pathway in CNS homeostasis and neurological disorders

Interferon Receptor Signaling in Malignancy: A Network of Cellular Pathways Defining Biological Outcomes

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