Cited by 241Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsNeuroinflammation and Neurodegeneration Mechanisms

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Cytokine Signaling Modulates Blood-Brain Barrier Function

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Pan, Weihong, P. Stone, Kirsten, Hsuchou, Hung, K. Manda, Vamshi, Zhang, Yan, J. Kastin, Abba·2011·Current Pharmaceutical Design

DOI 10.2174/138161211798220918PMC PMC3939622

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Abstract

The blood-brain barrier (BBB) provides a vast interface for cytokines to affect CNS function. The BBB is a target for therapeutic intervention. It is essential, therefore, to understand how cytokines interact with each other at the level of the BBB and how secondary signals modulate CNS functions beyond the BBB. The interactions between cytokines and lipids, however, have not been fully addressed at the level of the BBB. Here, we summarize current understanding of the localization of cytokine receptors and transporters in specific membrane microdomains, particularly lipid rafts, on the luminal (apical) surface of the microvascular endothelial cells composing the BBB. We then illustrate the clinical context of cytokine effects on the BBB by neuroendocrine regulation and amplification of inflammatory signals. Two unusual aspects discussed are signaling crosstalk by different classes of cytokines and genetic regulation of drug efflux transporters. We also introduce a novel area of focus on how cytokines may act through nuclear hormone receptors to modulate efflux transporters and other targets. A specific example discussed is the ATP-binding cassette transporter-1 (ABCA-1) that regulates lipid metabolism. Overall, cytokine signaling at the level of the BBB is a crucial feature of the dynamic regulation that can rapidly change BBB function and affect brain health and disease.

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Authors: Pan, W., P. Stone, K., Hsuchou, H., K. Manda, V., Zhang, Y., & J. Kastin, A.
Affiliations: Pennington Biomedical Research Center (US)
ORCID: Pan, Weihong
Zhang, Yan
Venue: Current Pharmaceutical Design
Publisher: Bentham Science Publishers Ltd.
Published: 2011-11-01
Volume: 17
Issue: 33
Pages: 3729-3740
ISSN: 1381-6128 (ISSN-L)
DOI: 10.2174/138161211798220918
PMC: PMC3939622
OpenAlex: W2042991023
Cited by: 241
References: 210
Citations by year: 2026: 15 · 2025: 16 · 2024: 19 · 2023: 23 · 2022: 24 · 2021: 25 · 2020: 29 · 2019: 20 · 2018: 22 · 2017: 12 · 2016: 8 · 2015: 16 · 2014: 6 · 2013: 4 · 2012: 2
FWCI: 0.34
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Current Pharmaceutical Design (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (DK54880)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-54880, R01DK054880, R56DK054880)
National Institute of Neurological Disorders and Stroke (NS62291, R01NS062291)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: blood-brain barrier, cytokine signaling, lipid rafts, cytokine receptors, efflux pumps, ABCA1, nuclear receptors, neuroinflammation, neuroendocrine regulation, signaling crosstalk, microvascular endothelial cells, lipid metabolism
MeSH terms: Animals, Blood-Brain Barrier, Carrier Proteins, Pharmaceutical Preparations, Humans, Inflammation, Ligands, Neuropeptides, Signal Transduction, Cytokines, Receptors, Cytoplasmic and Nuclear

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Cytokine Signaling Modulates Blood-Brain Barrier Function

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