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.
Keywords: Cytokines, blood-brain barrier, TNF, IL-15, leptin, adipokines, NFκB, STAT3, promoter analysis, ABCA-1, P-gp
Current Pharmaceutical Design
Title: Cytokine Signaling Modulates Blood-Brain Barrier Function
Volume: 17 Issue: 33
Author(s): Weihong Pan, Kirsten P. Stone, Hung Hsuchou, Vamshi K. Manda, Yan Zhang and Abba J. Kastin
Affiliation:
Keywords: Cytokines, blood-brain barrier, TNF, IL-15, leptin, adipokines, NFκB, STAT3, promoter analysis, ABCA-1, P-gp
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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Cite this article as:
Pan Weihong, P. Stone Kirsten, Hsuchou Hung, K. Manda Vamshi, Zhang Yan and J. Kastin Abba, Cytokine Signaling Modulates Blood-Brain Barrier Function, Current Pharmaceutical Design 2011; 17 (33) . https://dx.doi.org/10.2174/138161211798220918
DOI https://dx.doi.org/10.2174/138161211798220918 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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