Evidence map›Paper›PMID 34755124›Full record

ArticleBrain, behavior, & immunity - health2021

CCL4 induces inflammatory signalling and barrier disruption in the neurovascular endothelium.

Carolina Estevao, Chantelle E Bowers, Ding Luo, Mosharraf Sarker, Alexandra Eva Hoeh, Karen Frudd, Patric Turowski, John Greenwood

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

Article in Brain, behavior, & immunity - health, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 7% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Putative mechanisms of ocular inflammation in syphilis.Journal of ophthalmic inflammation and infection · 2026
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  9. Repurposing of Chemokine Antagonists for Combined Phase-Resolved Spinal Cord Injury Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  14. Targeting dysregulated CB1 receptors in a Down syndrome mouse model improves neurological outcomes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
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  17. Review
  18. Article
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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

8 authors at 1 institution in 1 country.

Carolina EstevaoInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Chantelle E BowersInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Ding LuoInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Mosharraf SarkerInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Alexandra Eva HoehInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Karen FruddInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
Patric TurowskiInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
John GreenwoodInstitute of Ophthalmology, University College London, 11-43 Bath Street, London, EC1V 9EL, UK.
University College London · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDuring neuroinflammation many chemokines alter the function of the blood-brain barrier (BBB) that regulates the entry of macromolecules and immune cells into the brain. As the milieu of the brain is altered, biochemical and structural changes contribute to the pathogenesis of neuroinflammation and may impact on neurogenesis. The chemokine CCL4, previously known as MIP-1β, is upregulated in a wide variety of central nervous system disorders, including multiple sclerosis, where it is thought to play a key role in the neuroinflammatory process. However, the effect of CCL4 on BBB endothelial cells (ECs) is unknown. MATERIALS AND

methodsExpression and distribution of CCR5, phosphorylated p38, F-actin, zonula occludens-1 (ZO-1) and vascular endothelial cadherin (VE-cadherin) were analysed in the human BBB EC line hCMEC/D3 by Western blot and/or immunofluorescence in the presence and absence of CCL4. Barrier modulation in response to CCL4 using hCMEC/D3 monolayers was assessed by measuring molecular flux of 70 ​kDa RITC-dextran and transendothelial lymphocyte migration. Permeability changes in response to CCL4

resultsCCR5, the receptor for CCL4, was expressed in hCMEC/D3 cells. CCL4 stimulation led to phosphorylation of p38 and the formation of actin stress fibres, both indicative of intracellular chemokine signalling. The distribution of junctional proteins was also altered in response to CCL4: junctional ZO-1 was reduced by

conclusionThese results show that CCL4 can modify BBB function and may contribute to disease pathogenesis.

Indexed as

BBB, blood-brain barrierCCL4ChemokinesCNS, central nervous systemEC, endothelial cellF-actin, filamentous actinhCMEC/D3, immortalized human cerebral microvascular endothelial cell lineInflammationMAPK, mitogen-activated protein kinaseNeurogenesisNeuroinflammationPermeabilitySDS-PAGE, Sodium dodecyl sulphate-polyacrylamide gel electrophoresisVE-cadherin, vascular endothelial cadherinZO-1, zonula occludens-1

Identifiers

PMID34755124
PMCPMC8560974
OpenAlexW3210410480

What Socratic 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 Socratic graph.