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Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier.
Neuroscience 2010; 166(2):408-15N

Abstract

There is accumulating evidence of the importance of cellular communication between the cells that compose the blood-brain barrier (BBB). Astrocytes are known to affect the expression of tissue-type plasminogen activator (t-PA) and its inhibitor plasminogen activator inhibitor type-1 (PAI-1) in endothelial cells. We investigated the influence of endothelial cells on astrocytic gene expression of PAI-1, protease nexin-1 (PN-1) and t-PA using an in vitro model of the BBB. Primary rat astrocyte-enriched cultures were cocultured with primary adult rat brain microvascular endothelial cells on opposite sides of a transwell membrane. After coculturing for 9-11 days, the cultures were treated with lipopolysaccharide (LPS) for 8 h or 24 h. The levels of PAI-1, PN-1 and t-PA mRNA in untreated and treated monocultures and cocultures were analyzed by Real-Time RT-PCR. Cocultivation of astrocytes and endothelial cells increased astrocytic PAI-1 mRNA expression, and this response was further amplified by LPS treatment. The levels of PN-1 and t-PA mRNA expression in astrocytes were unaffected by cocultivation and/or LPS treatment. Analysis of endothelial PAI-1 and t-PA gene expression revealed increased PAI-1 mRNA levels in cocultured cells, whereas t-PA mRNA levels remained unchanged. These results demonstrate that the cocultivation of astrocytes and endothelial cells induces a pronounced increase in astrocytic PAI-1 gene expression, and that this effect is amplified by LPS treatment. These findings imply an important role for intercellular crosstalk in modulating PAI-1 gene expression within the BBB, under both physiologic and pathophysiologic conditions.

Authors+Show Affiliations

Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. karin.hultman@neuro.gu.seNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20060032

Citation

Hultman, K, et al. "Potentiating Effect of Endothelial Cells On Astrocytic Plasminogen Activator Inhibitor Type-1 Gene Expression in an in Vitro Model of the Blood-brain Barrier." Neuroscience, vol. 166, no. 2, 2010, pp. 408-15.
Hultman K, Björklund U, Hansson E, et al. Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier. Neuroscience. 2010;166(2):408-15.
Hultman, K., Björklund, U., Hansson, E., & Jern, C. (2010). Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier. Neuroscience, 166(2), pp. 408-15. doi:10.1016/j.neuroscience.2010.01.002.
Hultman K, et al. Potentiating Effect of Endothelial Cells On Astrocytic Plasminogen Activator Inhibitor Type-1 Gene Expression in an in Vitro Model of the Blood-brain Barrier. Neuroscience. 2010 Mar 17;166(2):408-15. PubMed PMID: 20060032.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier. AU - Hultman,K, AU - Björklund,U, AU - Hansson,E, AU - Jern,C, Y1 - 2010/01/06/ PY - 2009/10/16/received PY - 2009/12/10/revised PY - 2010/01/03/accepted PY - 2010/1/12/entrez PY - 2010/1/12/pubmed PY - 2010/5/4/medline SP - 408 EP - 15 JF - Neuroscience JO - Neuroscience VL - 166 IS - 2 N2 - There is accumulating evidence of the importance of cellular communication between the cells that compose the blood-brain barrier (BBB). Astrocytes are known to affect the expression of tissue-type plasminogen activator (t-PA) and its inhibitor plasminogen activator inhibitor type-1 (PAI-1) in endothelial cells. We investigated the influence of endothelial cells on astrocytic gene expression of PAI-1, protease nexin-1 (PN-1) and t-PA using an in vitro model of the BBB. Primary rat astrocyte-enriched cultures were cocultured with primary adult rat brain microvascular endothelial cells on opposite sides of a transwell membrane. After coculturing for 9-11 days, the cultures were treated with lipopolysaccharide (LPS) for 8 h or 24 h. The levels of PAI-1, PN-1 and t-PA mRNA in untreated and treated monocultures and cocultures were analyzed by Real-Time RT-PCR. Cocultivation of astrocytes and endothelial cells increased astrocytic PAI-1 mRNA expression, and this response was further amplified by LPS treatment. The levels of PN-1 and t-PA mRNA expression in astrocytes were unaffected by cocultivation and/or LPS treatment. Analysis of endothelial PAI-1 and t-PA gene expression revealed increased PAI-1 mRNA levels in cocultured cells, whereas t-PA mRNA levels remained unchanged. These results demonstrate that the cocultivation of astrocytes and endothelial cells induces a pronounced increase in astrocytic PAI-1 gene expression, and that this effect is amplified by LPS treatment. These findings imply an important role for intercellular crosstalk in modulating PAI-1 gene expression within the BBB, under both physiologic and pathophysiologic conditions. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/20060032/Potentiating_effect_of_endothelial_cells_on_astrocytic_plasminogen_activator_inhibitor_type_1_gene_expression_in_an_in_vitro_model_of_the_blood_brain_barrier_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(10)00003-5 DB - PRIME DP - Unbound Medicine ER -