Evidence map›Paper›PMID 29751771›Full record

ArticleJournal of neuroinflammation2018

Unique and shared inflammatory profiles of human brain endothelia and pericytes.

Leon C D Smyth, Justin Rustenhoven, Thomas I-H Park, Patrick Schweder, Deidre Jansson, Peter A Heppner, Simon J O'Carroll, Edward W Mee, Richard L M Faull, Maurice Curtis and 1 more

Open access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

82 citing papers in PubMed, 137 citations in OpenAlex.

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22 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

11 authors at 2 institutions in 1 country.

Leon C D SmythDepartment of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Justin RustenhovenDepartment of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Thomas I-H ParkDepartment of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Patrick SchwederCentre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Deidre JanssonDepartment of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Peter A HeppnerCentre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Simon J O'CarrollCentre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Edward W MeeCentre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Richard L M FaullCentre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Maurice CurtisCentre for Brain Research, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
Mike DragunowDepartment of Pharmacology and Clinical Pharmacology, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand. m.dragunow@auckland.ac.nz.
University of Auckland · NZAuckland City Hospital · NZ

Funding

Health Research Council of New Zealand 16/608
6 · The paper itself

Abstract

backgroundPericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed.

methodsTo study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1β, TNFα, LPS, IFN-γ, TGF-β

resultsEndothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1β. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1β, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro.

conclusionsHere, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature.

Indexed as

Blood-Brain BarrierBrainCells, CulturedCoculture TechniquesEndothelial CellsHumansInflammationInflammation MediatorsPericytesInflammation MediatorsBlood-brain barrierGM-CSFIGFBPIL-1βNeuroinflammationNeurovascularSMAD2/3

Identifiers

PMID29751771
PMCPMC5948925
OpenAlexW2801530314

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.