Evidence map›Paper›PMID 25313834›Full record

ArticlePloS one2014

Interleukin-1β induces blood-brain barrier disruption by downregulating Sonic hedgehog in astrocytes.

Yue Wang, Shijie Jin, Yoshifumi Sonobe, Yi Cheng, Hiroshi Horiuchi, Bijay Parajuli, Jun Kawanokuchi, Tetsuya Mizuno, Hideyuki Takeuchi, Akio Suzumura

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 2 pooled it
7.7field-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

204 citing papers in PubMed, 2 syntheses or guidelines pooled it, 280 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. The Therapeutic Potential of Purmorphamine Across Disease Models.Journal of cellular and molecular medicine · 2026
    Review
  7. Review
  8. Article
  9. Heart Meets Brain: Insights into Neurocardiac Pathophysiology.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
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  11. Article
  12. Article
  13. Article
  14. Review
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  16. Article
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144 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

10 authors at 1 institution in 1 country.

Yue WangDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Shijie JinDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Yoshifumi SonobeDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Yi ChengDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Hiroshi HoriuchiDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Bijay ParajuliDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Jun KawanokuchiDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Tetsuya MizunoDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Hideyuki TakeuchiDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Akio SuzumuraDepartment of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Nagoya University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The blood-brain barrier (BBB) is composed of capillary endothelial cells, pericytes, and perivascular astrocytes, which regulate central nervous system homeostasis. Sonic hedgehog (SHH) released from astrocytes plays an important role in the maintenance of BBB integrity. BBB disruption and microglial activation are common pathological features of various neurologic diseases such as multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. Interleukin-1β (IL-1β), a major pro-inflammatory cytokine released from activated microglia, increases BBB permeability. Here we show that IL-1β abolishes the protective effect of astrocytes on BBB integrity by suppressing astrocytic SHH production. Astrocyte conditioned media, SHH, or SHH signal agonist strengthened BBB integrity by upregulating tight junction proteins, whereas SHH signal inhibitor abrogated these effects. Moreover, IL-1β increased astrocytic production of pro-inflammatory chemokines such as CCL2, CCL20, and CXCL2, which induce immune cell migration and exacerbate BBB disruption and neuroinflammation. Our findings suggest that astrocytic SHH is a potential therapeutic target that could be used to restore disrupted BBB in patients with neurologic diseases.

Indexed as

AnimalsAstrocytesBlood-Brain BarrierCell LineChemokinesDown-RegulationGene ExpressionHedgehog ProteinsInterleukin-1betaMiceParacrine CommunicationTight JunctionsChemokinesHedgehog ProteinsIL1B protein, mouseInterleukin-1betaShh protein, mouse

Identifiers

PMID25313834
PMCPMC4196962
OpenAlexW1974655099

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.