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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Hibiscus Sabdariffa Linnaeus (Malvaceae), Curcumin and Resveratrol as Alternative Medicinal Agents Against Metabolic Syndrome
Cardiovascular & Hematological Agents in Medicinal Chemistry Obesity in the Cardiovascular Continuum
Current Clinical Pharmacology New Inhibitors of Glycogen Phosphorylase as Potential Antidiabetic Agents
Current Medicinal Chemistry Evaluation of Pharmacological Treatment Strategies in Traumatic Brain Injury
Current Pharmaceutical Design Disorders of Respiration and Sleep-Disordered Breathing in Patients with Chronic Renal Failure
Current Respiratory Medicine Reviews Dietary Phytoestrogens: Neuroprotective Role in Parkinson’s Disease
Current Neurovascular Research Editorial A New Year of Excellence
Current Molecular Medicine The Effect of Prebiotic Products on Decreasing Adiposity Parameters in Overweight and Obese Individuals: A Systematic Review and Meta- Analysis
Current Medicinal Chemistry Antimicrobial and Antioxidant Properties of <i>Satureja Montana</i> L. and S. Subspicata Vis. (Lamiaceae)
Current Drug Targets Preparation and Characterization of Spray-Dried Mucoadhesive Microspheres of Ketorolac for Nasal Administration
Current Drug Delivery Editorial [Hot topic: MHC and MHC-Like Molecules in the Design of Vaccines (Executive Editor: Vasso Apostolopoulos)]
Current Pharmaceutical Design Air Pollution, Platelet Activation and Atherosclerosis
Inflammation & Allergy - Drug Targets (Discontinued) Data Analysis-Driven Precise Asthmatic Treatment by Targeting Mast Cells
Endocrine, Metabolic & Immune Disorders - Drug Targets MRP1-dependent Collateral Sensitivity of Multidrug-resistant Cancer Cells: Identifying Selective Modulators Inducing Cellular Glutathione Depletion
Current Medicinal Chemistry Tumor Stroma Manipulation By MSC
Current Drug Targets Treatment of Acute Leukaemias with Monoclonal Antibodies: Current Status and Future Prospects
Cardiovascular & Hematological Agents in Medicinal Chemistry Necroptosis: Who Knew There were so Many Interesting Ways to Die?
CNS & Neurological Disorders - Drug Targets Targeted Biomedical Treatment for Autism Spectrum Disorders
Current Pharmaceutical Design Murabutide Revisited: A Review of its Pleiotropic Biological Effects
Current Medicinal Chemistry Pleasure as an Overlooked Target of Substance Use Disorder Research and Treatment
Current Drug Abuse Reviews