Evidence map›Paper›PMID 29973684›Full record

ArticleScientific reports2018

The functional and inflammatory response of brain endothelial cells to Toll-Like Receptor agonists.

Rebecca H Johnson, Dan T Kho, Simon J O' Carroll, Catherine E Angel, E Scott Graham

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

21 citing papers in PubMed, 43 citations in OpenAlex.

  1. Kinin BPharmaceuticals (Basel, Switzerland) · 2025
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  10. Opioid Use, Gut Dysbiosis, Inflammation, and the Nervous System.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022
    Review
  11. Article
  12. Viral mimetic triggers cerebral arteriopathy in juvenile brain via neutrophil elastase and NETosis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Article
  13. SARS-CoV-2: is there neuroinvasion?Fluids and barriers of the CNS · 2021
    Review
  14. Article
  15. Review
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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

5 authors at 3 institutions in 1 country.

Rebecca H JohnsonCentre for Brain Research, Auckland, New Zealand.
Dan T KhoCentre for Brain Research, Auckland, New Zealand.
Simon J O' CarrollCentre for Brain Research, Auckland, New Zealand.
Catherine E AngelSchool of Biological Sciences, Faculty of Science, University of Auckland, Auckland, New Zealand.
E Scott GrahamCentre for Brain Research, Auckland, New Zealand. s.graham@auckland.ac.nz.
Brain Research New Zealand · NZPharmac · NZUniversity of Auckland · NZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Toll-Like receptors (TLRs) represent an important early warning mechanism for the immune system to detect infection or tissue damage. The focus of this research was to determine the neuroinflammatory responses to commercial TLR ligands and their effects on brain endothelial barrier strength. Using biosensor technology we screened TLR ligands to all human TLRs and found that the brain endothelial hCMVECs cell line only responded to Poly(I:C) (TLR3-ligand), LPS (TLR4-ligand) and Imiquimod (TLR7 ligand). Both Poly(I:C) and LPS induced pronounced pro-inflammatory cytokine secretion as expected, whereas Imiquimod did not induce secretion of any pro-inflammatory cytokines. Using ECIS technology to measure endothelial barrier function, LPS and Poly(I:C) both acutely reduced barrier-strength, whereas Imiquimod caused immediate and sustained strengthening of the barrier. Further cytokine and ECIS studies showed that Imiquimod could abrogate some of the pro-inflammatory responses to Poly(I:C) and LPS. Most surprisingly, PCR revealed that the hCMVECs lacked TLR7 but expressed both TLR3 and TLR4 and did not respond to other structurally different TLR7 ligands. These data demonstrate that brain endothelial cells can be regulated by TLR 3 and TLR4 ligands in a pro-inflammatory manner and have receptors to Imiquimod, distinct to the classical TLR7, that function in an anti-inflammatory manner.

Indexed as

Biosensing TechniquesBlood-Brain BarrierCell LineCytokinesEndothelial CellsHumansImiquimodLipopolysaccharidesPoly I-CToll-Like ReceptorsCytokinesImiquimodLipopolysaccharidesPoly I-CToll-Like Receptors

Identifiers

PMID29973684
PMCPMC6031625
OpenAlexW2810534926

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.