Evidence map›Paper›PMID 26043079›Full record

ArticleCell death & disease2015

Microglia-derived IL-1β triggers p53-mediated cell cycle arrest and apoptosis in neural precursor cells.

J Guadagno, P Swan, R Shaikh, S P Cregan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
7.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 133 citations in OpenAlex.

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    Article
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

J GuadagnoDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
P SwanDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
R ShaikhDepartment of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
S P Cregan1] Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada [2] Robarts Research Institute, University of Western Ontario, London, ON, Canada.
Western University · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

Neurogenesis persists in the adult brain and can contribute to learning and memory processes and potentially to regeneration and repair of the affected nervous system. Deregulated neurogenesis has been observed in neuropathological conditions including neurodegenerative diseases, trauma and stroke. However, the survival of neural precursor cells (NPCs) and newly born neurons is adversely affected by the inflammatory environment that arises as a result of microglial activation associated with injury or disease processes. In the present study, we have investigated the mechanisms by which microglia affect NPC proliferation and survival. Importantly, we demonstrate that interleukin-1β (IL-1β) produced by lipopolysaccharide/interferon-γ-activated microglia is necessary to induce cell cycle arrest and apoptosis in NPCs in vitro. Mechanistically, we show that IL-1β activates the tumor suppressor p53 through an oxidative stress-dependent mechanism resulting in p53-mediated induction of the cyclin-dependent kinase inhibitor p21 and the proapoptotic Bcl-2 (B-cell lymphoma-2) family members Puma (p53-upregulated modulator of apoptosis) and Noxa. Furthermore, we demonstrate that cell cycle arrest and apoptosis induced by recombinant IL-1β or activated microglia is attenuated in p53-deficient NPCs. Finally, we have determined that IL-1β induces NPC death via the p53-dependent induction of Puma leading to the activation of a Bax (Bcl-2-associated X protein)-mediated mitochondrial apoptotic pathway. In summary, we have elucidated a novel role for p53 in the regulation of NPC proliferation and survival during neuroinflammatory conditions that could be targeted to promote neurogenesis and repair in a number of neurological conditions.

Indexed as

AnimalsApoptosisApoptosis Regulatory Proteinsbcl-2-Associated X ProteinCell Cycle CheckpointsCells, CulturedCyclin-Dependent Kinase Inhibitor p21Enzyme ActivationInterferon-gammaInterleukin-1betaLipopolysaccharidesMiceMice, KnockoutMicrogliaMitochondriaNerve RegenerationApoptosis Regulatory ProteinsBBC3 protein, humanbcl-2-Associated X ProteinCyclin-Dependent Kinase Inhibitor p21IL1B protein, humanInterferon-gammaInterleukin-1betaLipopolysaccharidesPMAIP1 protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Recombinant ProteinsTumor Suppressor Protein p53

Identifiers

PMID26043079
PMCPMC4669832
OpenAlexW1551854884

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.