RGD Reference Report - Impact of astrocyte and lymphocyte interactions on the blood-brain barrier in multiple sclerosis. - Rat Genome Database

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Impact of astrocyte and lymphocyte interactions on the blood-brain barrier in multiple sclerosis.

Authors: Yan, X-B  Zhao, Y-F  Yang, Y-M  Wang, N  He, B-Z  Qiu, X-T 
Citation: Yan XB, etal., Rev Neurol (Paris). 2019 Jun;175(6):396-402. doi: 10.1016/j.neurol.2018.12.006. Epub 2019 Apr 23.
RGD ID: 38549575
Pubmed: PMID:31027862   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neurol.2018.12.006   (Journal Full-text)


OBJECTIVE: This study was designed to investigate the impact of astrocyte and lymphocyte (LC) interactions in the blood-brain barrier (BBB) on the pathogenesis of multiple sclerosis (MS).
METHODS: Primary rat brain microvascular endothelial cells (rBMECs) and astrocytes isolated from Sprague-Dawley rats were used to establish in vitro BBB models. Transendothelial electrical resistance (TEER) and permeability were compared between rBMEC monocultures and rBMEC/astrocyte co-cultures to evaluate the validity of each as a BBB cell model. rBMEC/LC co-cultures and rBMEC/astrocyte/LC tri-cultures were established to evaluate inflammatory responses in MS by measuring the gene expression levels of nerve growth factor (NGF), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), interleukin 17 (IL-17), interferon γ (IFN-γ), and forkhead box P3 (Foxp3).
RESULTS: The rBMEC/astrocyte co-cultures exhibited higher TEER values and lower lymphocyte permeabilities than those of rBMEC monocultures. Compared to the rBMEC mono-cultures, the rBMEC/astrocyte/LC tri-cultures showed significantly decreased NGF, IL-17, and IFN-γ and increased MMP-2 and Foxp3 expression. Furthermore, the tri-cultures exhibited decreased NGF, IL-17, and IFN-γ expression compared to the rBMEC/astrocyte co-cultures, and increased MMP-2 expression compared to that shown by the rBMEC/LC co-cultures. MMP-9 expression did not vary significantly between the four established BBB cell models.
CONCLUSION: These results suggest that the synergistic effect between astrocytes and LCs may increase the expression of MMP-2 and decrease that of IL-17 and IFN-γ at the BBB. Furthermore, the use of rBMEC/astrocytes/LC tri-cultures enabled us to test the synergistic effect between astrocytes and LCs and their roles in MS pathogenesis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
establishment of endothelial blood-brain barrier  IEP 38549575 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Foxp3  (forkhead box P3)


Additional Information