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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Pan, W., Banks, W. A., Kennedy, M., Gutierrez, E. G., & Kastin, A. J. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.271.4.e636 · Cited by 127
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Clathrin-independent endocytosis: New insights into caveolae and non-caveolar lipid raft carriers
Kirkham, M., & Parton, R. G. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2005.11.007 · Cited by 127
Claudin-5 as a Novel Estrogen Target in Vascular Endothelium
Burek, M., Arias-Loza, P.-A., Roewer, N., & Förster, C. Y. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.197582 · Cited by 125
Interleukin-1β-mediated Suppression of RXR:RAR Transactivation of the Ntcp Promoter Is JNK-dependent
Li, D., Zimmerman, T. L., Thevananther, S., Lee, H., Kurie, J. M., & Karpen, S. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204818200 · Cited by 125
Clathrin‐independent endocytosis used by the IL‐2 receptor is regulated by Rac1, Pak1 and Pak2
Grassart, A., Dujeancourt-Henry, A., Lazarow, P. B., Dautry‐Varsat, A., & Sauvonnet, N. (2008) · EMBO Reports · doi:10.1038/embor.2008.28 · Cited by 123
Lipid Rafts and Caveolin-1 Coordinate Interleukin-1β (IL-1β)-dependent Activation of NFκB by Controlling Endocytosis of Nox2 and IL-1β Receptor 1 from the Plasma Membrane
Oakley, F. D., Smith, R. L., & Engelhardt, J. F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.042127 · Cited by 120
Passage of peptides across the blood-brain barrier: Pathophysiological perspectives
Banks, W. A., & Kastin, A. J. (1996) · Life Sciences · doi:10.1016/s0024-3205(96)00380-3 · Cited by 120
Unidirectional Specific and Modulated Brain to Blood Transport of Corticotropin-Releasing Hormone
Martins, M., Kastin, A. J., & Banks, W. A. (2008) · Neuroendocrinology · doi:10.1159/000126974 · Cited by 119
Nonsaturable entry of neuropeptide Y into brain
Kastin, A. J., & Akerstrom, V. L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.3.e479 · Cited by 119
Adipokines and the blood-brain barrier
Pan, W., & Kastin, A. J. (2007) · Peptides · doi:10.1016/j.peptides.2007.04.023 · Cited by 118
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Leptin transport across the blood–brain barrier of the Koletsky rat is not mediated by a product of the leptin receptor gene
Banks, W. A., Niehoff, M. L., Martin, D., & Farrell, C. L. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03013-5 · Cited by 118
Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses of microglia and astrocytes
Zhang-Gandhi, C. X., & Drew, P. D. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.11.007 · Cited by 117
Physiological Pathway for Low-Density Lipoproteins across the Blood-Brain Barrier: Transcytosis through Brain Capillary Endothelial Cells In Vitro
Candela, P., Gosselet, F., Miller, F., Buee-Scherrer, V., Torpier, G., Cecchelli, R., & Fenart, L. (2008) · Endothelium · doi:10.1080/10623320802487759 · Cited by 117
Cytokines Stimulate the CRH but Not the Vasopressin Neuronal System: Evidence for a Median Eminence Site of Interleukin-6 Action
Spinedi, E., Hadid, R., Daneva, T., & Gaillard, R. C. (2008) · Neuroendocrinology · doi:10.1159/000126207 · Cited by 115
Involvement of the Ubiquitin/Proteasome System in Sorting of the Interleukin 2 Receptor β Chain to Late Endocytic Compartments
Rocca, A., Lamaze, C., Subtil, A., & Dautry‐Varsat, A. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.5.1293 · Cited by 113
Get Off My Back! Rapid Receptor Internalization through Circular Dorsal Ruffles
Orth, J. D., & McNiven, M. A. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-3397 · Cited by 112
Site-specific Androgen Receptor Serine Phosphorylation Linked to Epidermal Growth Factor-dependent Growth of Castration-recurrent Prostate Cancer
Ponguta, L. A., Gregory, C. W., French, F. S., & Wilson, E. M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802392200 · Cited by 112
Distribution of 3H-α-MSH in rat brain
Kastin, A. J., Nissen, C., Nikolics, K., Medzihradszky, K., Coy, D. H., Teplán, I., & Schally, A. V. (1976) · Brain Research Bulletin · doi:10.1016/0361-9230(76)90045-9 · Cited by 112
Filamin A Regulates Caveolae Internalization and Trafficking in Endothelial Cells
Sverdlov, M. S., Shinin, V., Place, A. T., Castellon, M., & Minshall, R. D. (2009) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-10-0997 · Cited by 110
MyD88 signaling in brain endothelial cells is essential for the neuronal activity and glucocorticoid release during systemic inflammation
Gosselin, D., & Rivest, S. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002122 · Cited by 109
PPARα and PPARγ attenuate HIV‐induced dysrégulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities
Huang, W., Eum, S. Y., Andras, I. E., Hennig, B., & Toborek, M. J. (2009) · The FASEB Journal · doi:10.1096/fj.08-121624 · Cited by 109
Caveolae Participate in Tumor Necrosis Factor Receptor 1 Signaling and Internalization in a Human Endothelial Cell Line
D’Alessio, A., Al‐Lamki, R. S., Bradley, J. R., & Pober, J. S. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)62346-2 · Cited by 108
Regulation of major efflux transporters under inflammatory conditions at the blood‐brain barrierin vitro
von Wedel-Parlow, M., Wölte, P., & Galla, H. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06305.x · Cited by 106
Blood–Brain Barrier Permeability to Ebiratide and TNF in Acute Spinal Cord Injury
Pan, W., Banks, W. A., & Kastin, A. J. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6533 · Cited by 106
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Activation of Peroxisome Proliferator-Activated Receptor γ (PPARγ) Suppresses Rho GTPases in Human Brain Microvascular Endothelial Cells and Inhibits Adhesion and Transendothelial Migration of HIV-1 Infected Monocytes
Ramirez, S. H., Heilman, D., Morsey, B., Potula, R., Haorah, J., & Persidsky, Y. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.3.1854 · Cited by 105
Entry of EGF into brain is rapid and saturable
Pan, W., & Kastin, A. J. (1999) · Peptides · doi:10.1016/s0196-9781(99)00094-7 · Cited by 104
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Functional and morphological studies of protein transcytosis in continuous endothelia
Predescu, D. N., Vogel, S. M., & Malik, A. B. (2004) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00075.2004 · Cited by 102
Dexamethasone induces the expression of metalloproteinase inhibitor TIMP‐1 in the murine cerebral vascular endothelial cell line cEND
Förster, C. Y., Kahles, T., Kietz, S., & Drenckhahn, D. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.129007 · Cited by 102
Effect of endotoxin on expression of TNF receptors and transport of TNF-α at the blood-brain barrier of the rat
Osburg, B., Peiser, C., Dömling, D., Schomburg, L., Ko, Y., Voigt, K., & Bickel, U. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00436.2001 · Cited by 100
P-glycoprotein on astrocyte foot processes of unfixed isolated human brain capillaries
Golden, P. L., & Pardridge, W. M. (1999) · Brain Research · doi:10.1016/s0006-8993(98)01305-5 · Cited by 98
Glucocorticoid effects on mouse microvascular endothelial barrier permeability are brain specific
Förster, C. Y., Waschke, J., Burek, M., Leers, J., & Drenckhahn, D. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.106385 · Cited by 97
Passage of human amyloid β-protein 1–40 across the murine blood-brain barrier
Maness, L. M., Banks, W. A., Podlisny, M. B., Selkoe, D. J., & Kastin, A. J. (1994) · Life Sciences · doi:10.1016/0024-3205(94)00331-9 · Cited by 97
Soluble receptor inhibits leptin transport
Tu, H., Kastin, A. J., Hsuchou, H., & Pan, W. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21195 · Cited by 96
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The Blood-Brain Barrier in NeuroAIDS
Banks, W. A., Nuran Ercal, A., & Price, T. O. (2006) · Current HIV Research · doi:10.2174/157016206777709447 · Cited by 95
Rate of 59Fe Uptake into Brain and Cerebrospinal Fluid and the Influence Thereon of Antibodies Against the Transferrin Receptor
Ueda, F., Raja, K. B., Simpson, R. J., Trowbridge, I. S., & Bradbury, M. W. B. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb05828.x · Cited by 94
Studies of the slow bidirectional transport of iron and transferrin across the blood-brain barrier
Banks, W. A., Kastin, A. J., Fasold, M. B., Barrera, C. M., & Augereau, G. (1988) · Brain Research Bulletin · doi:10.1016/0361-9230(88)90021-4 · Cited by 93
Urocortin and the brain
Pan, W., & Kastin, A. J. (2007) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2007.10.008 · Cited by 92
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Steroid receptor phosphorylation: Assigning function to site‐specific phosphorylation
Ward, R. D., & Weigel, N. L. (2009) · BioFactors · doi:10.1002/biof.66 · Cited by 92
Efflux of human and mouse amyloid β proteins 1–40 and 1–42 from brain: impairment in a mouse model of alzheimer's disease
Banks, W. A., Robinson, S. M., Verma, S., & Morley, J. E. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00474-3 · Cited by 92
Ethanol mimics ligand‐mediated activation and endocytosis of IL‐1RI/TLR4 receptors via lipid rafts caveolae in astroglial cells
Blanco, A. M. A., Pérez-Aragó, A., Fernández‐Lizarbe, S., & Guerri, C. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05425.x · Cited by 92
Expression of endothelial phosphorylated caveolin‐1 is increased in brain injury
Nag, S., Manias, J. L., & Stewart, D. J. (2009) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2008.01009.x · Cited by 90
Circulating Regulatory Factors and Neuroendocrine Function
Porter, J. C., & Ježová, D. (1990) · Advances in experimental medicine and biology · doi:10.1007/978-1-4684-5799-5 · Cited by 89
Linkage of progestin and epidermal growth factor signaling: Phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth
Daniel, A. R., Qiu, M., Faivre, E. J., Ostrander, J. H., Skildum, A. J., & Lange, C. A. (2006) · Steroids · doi:10.1016/j.steroids.2006.11.009 · Cited by 87
Regulation of transendothelial permeability by Src Kinase
Hu, G., & Minshall, R. D. (2008) · Microvascular Research · doi:10.1016/j.mvr.2008.10.002 · Cited by 87
Functional Expression of P-glycoprotein in Rat Brain Microglia
Lee, G. S., Schlichter, L. C., Bendayan, M., & Bendayan, R. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29319-8 · Cited by 87
Upregulation of Tumor Necrosis Factor α Transport across the Blood–Brain Barrier after Acute Compressive Spinal Cord Injury
Pan, W., Kastin, A. J., Bell, R. L., & Olson, R. D. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-09-03649.1999 · Cited by 85
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Glucose and Insulin Increase the Transport of Leptin through the Blood-Brain Barrier in Normal Mice but Not in Streptozotocin-Diabetic Mice
Kastin, A. J., & Akerstrom, V. L. (2001) · Neuroendocrinology · doi:10.1159/000054640 · Cited by 85
Pak1 Phosphorylation Enhances Cortactin-N-WASP Interaction in Clathrin-Caveolin-Independent Endocytosis
Grassart, A., Meas‐Yedid, V., Dufour, A., Olivo‐Marín, J., Dautry‐Varsat, A., & Sauvonnet, N. (2010) · Traffic · doi:10.1111/j.1600-0854.2010.01075.x · Cited by 82
Interleukin-1α in blood has direct access to cortical brain cells
Banks, W. A., Kastin, A. J., & Gutierrez, E. G. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90224-9 · Cited by 82
Leptin receptor mRNA in rat brain astrocytes
Hsuchou, H., Pan, W., Barnes, M. J., & Kastin, A. J. (2009) · Peptides · doi:10.1016/j.peptides.2009.08.023 · Cited by 78
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Neuroinflammation facilitates LIF entry into brain: role of TNF
Pan, W., Yu, C., Hsuchou, H., Zhang, Y., & Kastin, A. J. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00489.2007 · Cited by 77
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Validity of multiple-time regression analysis in measurement of tritiated and iodinated leptin crossing the blood-brain barrier: meaningful controls
Kastin, A. J., Akerstrom, V. L., & Pan, W. (2001) · Peptides · doi:10.1016/s0196-9781(01)00569-1 · Cited by 75
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Opposite direction of transport across the blood-brain barrier for Tyr-MIF-1 and MIF-1: Comparison with morphine
Banks, W. A., & Kastin, A. J. (1994) · Peptides · doi:10.1016/0196-9781(94)90165-1 · Cited by 74
Oxysterol Activators of Liver X Receptor and 9-cis-Retinoic Acid Promote Sequential Steps in the Synthesis and Secretion of Tumor Necrosis Factor-α from Human Monocytes
Landis, M. S., Patel, H. V., & Capone, J. P. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108807200 · Cited by 74
Diurnal variation of leptin entry from blood to brain involving partial saturation of the transport system
Pan, W., & Kastin, A. J. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01085-2 · Cited by 73
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Progesterone exerts neuroprotective effects by inhibiting inflammatory response after stroke
Jiang, C. Q., Wang, J., Li, X., Liu, C., Chen, N., & Hao, Y. (2009) · Inflammation Research · doi:10.1007/s00011-009-0032-8 · Cited by 73
Functions of lipid raft membrane microdomains at the blood–brain barrier
Dodelet-Devillers, A., Cayrol, R., van Horssen, J., Haqqani, A. S., de Vries, H. E., Engelhardt, B., Greenwood, J., & Prat, A. (2009) · Journal of Molecular Medicine · doi:10.1007/s00109-009-0488-6 · Cited by 71
Developmental Changes of Leptin Receptors in Cerebral Microvessels: Unexpected Relation to Leptin Transport
Pan, W., Hsuchou, H., Tu, H., & Kastin, A. J. (2007) · Endocrinology · doi:10.1210/en.2007-0893 · Cited by 70
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Changing the chemokine gradient: CINC1 crosses the blood–brain barrier
Pan, W., & Kastin, A. J. (2001) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(01)00256-9 · Cited by 70
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Fasting, but not adrenalectomy, reduces transport of leptin into the brain☆
Kastin, A. J., & Akerstrom, V. L. (2000) · Peptides · doi:10.1016/s0196-9781(00)00195-9 · Cited by 70
Endocytic pathway of recombinant murine tumor necrosis factor in L-929 cells.
Mosselmans, R., Hepburn, A., Dumont, J. E., Fiers, W., & Galand, P. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.141.9.3096 · Cited by 69
Saturable entry of leukemia inhibitory factor from blood to the central nervous system
Pan, W., Kastin, A. J., & Brennan, J. M. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(00)00241-1 · Cited by 68
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HIV-1 infected monocyte-derived macrophages affect the human brain microvascular endothelial cell proteome: New insights into blood–brain barrier dysfunction for HIV-1-associated dementia
Ricardo-Dukelow, M., Kadiu, I., Rożek, W., Schlautman, J. D., Persidsky, Y., Ciborowski, P. S., Kanmogne, G. D., & Gendelman, H. E. (2007) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2007.01.004 · Cited by 67
Stroke upregulates TNFα transport across the blood–brain barrier
Pan, W., Ding, Y., Yu, Y., Ohtaki, H., Nakamachi, T., & Kastin, A. J. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2005.11.020 · Cited by 67
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Chronic Inflammatory Pain and the Neurovascular Unit: A Central Role for Glia in Maintaining BBB Integrity?
Willis, C. L., & Davis, T. P. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208784705414 · Cited by 66
Selective increase in TNFα permeation across the blood–spinal cord barrier after SCI
Pan, W., Zhang, L., Liao, J., Csernus, B., & Kastin, A. J. (2003) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00426-5 · Cited by 65
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Strategy and mechanism for the prevention of hepatocellular carcinoma: Phosphorylated retinoid X receptor α is a critical target for hepatocellular carcinoma chemoprevention
Shimizu, M., Takai, K., & Moriwaki, H. (2008) · Cancer Science · doi:10.1111/j.1349-7006.2008.01045.x · Cited by 65
Cloning and characterization of the murine claudin-5 promoter
Burek, M., & Förster, C. Y. (2008) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2008.09.041 · Cited by 64
Increase in TNFα Transport after SCI Is Specific for Time, Region, and Type of Lesion
Pan, W., & Kastin, A. J. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7702 · Cited by 64
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Increased hippocampal uptake of tumor necrosis factor α and behavioral changes in mice
Pan, W., Kastin, A. J., Rigai, T., McLay, R. N., & Pick, C. G. (2003) · Experimental Brain Research · doi:10.1007/s00221-002-1355-7 · Cited by 64
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Peroxisome Proliferator-Activated Receptor-α Activation Protects Brain Capillary Endothelial Cells from Oxygen-Glucose Deprivation-Induced Hyperpermeability in the Blood-Brain Barrier
Mysiorek, C., Culot, M., Dehouck, L., Derudas, B., Staels, B., Bordet, R., Cecchelli, R., Fénart, L., & Bérézowski, V. (2009) · Current Neurovascular Research · doi:10.2174/156720209788970081 · Cited by 64
TNF Activates P-Glycoprotein in Cerebral Microvascular Endothelial Cells
Yu, C., Kastin, A. J., Tu, H., Waters, S., & Pan, W. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000110445 · Cited by 64
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Saturable entry of ciliary neurotrophic factor into brain
Pan, W., Kastin, A. J., Maness, L. M., & Brennan, J. M. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00083-x · Cited by 63
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Blood‐borne interleukin‐1 alpha is transported across the endothelial blood‐spinal cord barrier of mice.
Banks, W. A., Kastin, A. J., & Ehrensing, C. A. (1994) · The Journal of Physiology · doi:10.1113/jphysiol.1994.sp020293 · Cited by 63
Activation of urocortin transport into brain by leptin
Kastin, A. J., Akerstrom, V. L., & Pan, W. (2000) · Peptides · doi:10.1016/s0196-9781(00)00349-1 · Cited by 61
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Differential Interactions of Urocortin/Corticotropin-Releasing Hormone Peptides with the Blood-Brain Barrier
Kastin, A. J., & Akerstrom, V. L. (2002) · Neuroendocrinology · doi:10.1159/000059433 · Cited by 58
Regulatory effects of synthetic liver X receptor- and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells
Panzenboeck, U., Kratzer, I., Sovic, A., Wintersperger, A., Bernhart, E. M., Hammer, A., Malle, E., & Sattler, W. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2006.01.013 · Cited by 57
HIV-1-induced production of endothelin-1 in an in vitro model of the human blood???brain barrier
Didier, N., Banks, W. A., ́minon, C. C., Dereuddre‐Bosquet, N., & Mabondzo, A. M. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00022 · Cited by 56
Biphasic cytoarchitecture and functional changes in the BBB induced by chronic inflammatory pain
Brooks, T. A., Ocheltree, S. M., Seelbach, M. J., Charles, R., Nametz, N., Egleton, R. D., & Davis, T. P. (2006) · Brain Research · doi:10.1016/j.brainres.2006.08.085 · Cited by 55
Drug Delivery to Brain and the Role of Carrier-Mediated Transport
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Phosphorylation of the Retinoid X Receptor at the Omega loop, modulates the expression of retinoic-acid-target genes with a promoter context specificity
Bruck, N., Bastien, J., Bour, G., Tarrade, A., Plassat, J.-L., Bauer, A., Adam-Stitah, S., & Rochette-Egly, C. (2005) · Cellular Signalling · doi:10.1016/j.cellsig.2004.12.006 · Cited by 52
Entry of CART into brain is rapid but not inhibited by excess CART or leptin
Kastin, A. J., & Akerstrom, V. L. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.5.e901 · Cited by 52
Convergent trafficking pattern of leptin after endocytosis mediated by ObRa–ObRd
Tu, H., Pan, W., Feucht, L., & Kastin, A. J. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21020 · Cited by 50
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ATP-binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-β peptide (1–40) at the blood–brain barrier
Akanuma, S.-I., Ohtsuki, S., Doi, Y., Tachikawa, M., Ito, S., Hori, S., Asashima, T., Hashimoto, T., Yamada, K., Ueda, K., et al. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.12.002 · Cited by 50
Agouti-related protein(83-132) aggregates and crosses the blood-brain barrier slowly
Kastin, A. J., Akerstrom, V. L., & Hackler, L. (2000) · Metabolism · doi:10.1053/meta.2000.16556 · Cited by 50
Neuroinflammation Activates Mdr1b Efflux Transport Through NFκB: Promoter Analysis in BBB Endothelia
Yu, C., Argyropoulos, G. A., Zhang, Y., Kastin, A. J., Hsuchou, H., & Pan, W. (2008) · Cellular Physiology and Biochemistry · doi:10.1159/000185558 · Cited by 49
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Decreased blood–brain leptin transfer in an ovine model of obesity and weight loss: resolving the cause of leptin resistance
Adam, C. L., & Findlay, P. A. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.28 · Cited by 46
Peptides and the Blood–Brain Barrier: The Status of Our Understanding
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In vitro demonstration of a saturable transport system for leptin across the blood-brain barrier
Maresh, G. A., Maness, L. M., Zadina, J. E., & Kastin, A. J. (2001) · Life Sciences · doi:10.1016/s0024-3205(01)01093-1 · Cited by 44
Cytokine Transport Across the Injured Blood-Spinal Cord Barrier
Pan, W., & Kastin, A. J. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208784705450 · Cited by 44
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Receptor-mediated transport of LIF across blood–spinal cord barrier is upregulated after spinal cord injury
Pan, W., Cain, C. M., Yu, Y., & Kastin, A. J. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.02.006 · Cited by 44
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LIVER X RECEPTOR AGONIST GW3965 DOSE-DEPENDENTLY REGULATES LPS-MEDIATED LIVER INJURY AND MODULATES POSTTRANSCRIPTIONAL TNF-α PRODUCTION AND P38 MITOGEN-ACTIVATED PROTEIN KINASE ACTIVATION IN LIVER MACROPHAGES
Wang, Y. Y., Dahle, M. K., Steffensen, K. R., Reinholt, F. P., Collins, J. L., Thiemermann, C., Aasen, A. O., Gustafsson, J.-Α., & Wang, J. E. (2009) · Shock · doi:10.1097/shk.0b013e3181a47f85 · Cited by 43
Expression of nuclear receptor mRNA and liver X receptor-mediated regulation of ABC transporter A1 at rat blood–brain barrier
Akanuma, S.-I., Hori, S., Ohtsuki, S., Fujiyoshi, M., & Terasaki, T. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.08.012 · Cited by 43
Upregulation of the Transport System for TNFa at the Blood-Brain Barrier
Pan, W., & Kastin, A. J. (2001) · Archives of Physiology and Biochemistry · doi:10.1076/apab.109.4.350.4238 · Cited by 43
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Upregulation of p55 and p75 Receptors Mediating TNF-α Transport Across the Injured Blood-Spinal Cord Barrier
Pan, W., Csernus, B., & Kastin, A. J. (2003) · Journal of Molecular Neuroscience · doi:10.1385/jmn:21:2:173 · Cited by 41
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Melanocortin potentiates leptin‐induced STAT3 signaling via MAPK pathway
Zhang, Y., Wu, X., He, Y., Kastin, A. J., Hsuchou, H., Rosenblum, C. I., & Pan, W. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06144.x · Cited by 41
Self-citation
A biophysical approach to IL-2 and IL-15 receptor function: Localization, conformation and interactions
Bodnár, A., Nizsalóczki, E., Mocsár, G., Szalóki, N., Waldmann, T. A., Damjanovich, S., & Vámosi, G. (2008) · Immunology Letters · doi:10.1016/j.imlet.2007.12.014 · Cited by 41
Reversible association of the cytokines MIP-1α and MIP-1β with the endothelia of the blood-brain barrier
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Circulating TGF-β1 Does Not Cross the Intact Blood-Brain Barrier
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Self-citation
Cytokine signaling in the human brain capillary endothelial cell line hCMEC/D3
Fasler‐Kan, E., Suenderhauf, C., Barteneva, N. S., Poller, B., Gygax, D., & Huwyler, J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.077 · Cited by 40
Essential Role for Membrane Lipid Rafts in Interleukin-1β−Induced Nitric Oxide Release From Insulin-Secreting Cells
Veluthakal, R., Chvyrkova, I., Tannous, M., McDonald, P., Amin, R., Hadden, T. J., Thurmond, D. C., Quon, M. J., & Kowluru, A. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2576 · Cited by 39
Unique leptin trafficking by a tailless receptor
Tu, H., Hsuchou, H., Kastin, A. J., Wu, X., & Pan, W. (2010) · The FASEB Journal · doi:10.1096/fj.09-143487 · Cited by 39
Self-citation
Temporal expression of IL-1β protein and mRNA in the brain after systemic LPS injection is affected by age and estrogen
Johnson, A. B., Bake, S., Lewis, D. K., & Sohrabji, F. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2006.01.019 · Cited by 38
Modulation of feeding‐related peptide/protein signals by the blood–brain barrier
Pan, W., Akerstrom, V. L., Zhang, J., Pejović, V., & Kastin, A. J. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02502.x · Cited by 38
Self-citation
Binding, internalization, and membrane incorporation of human immunodeficiency virus-1 at the blood–brain barrier is differentially regulated
Banks, W. A., Robinson, S. M., Wolf, K. M., Bess, J. W., & Arthur, L. O. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.06.021 · Cited by 38
Phe13, Tyr19‐Melanin‐Concentrating Hormone and the Blood—Brain Barrier
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TGFα and the Blood–Brain Barrier: Accumulation in Cerebral Vasculature
Pan, W., Vallance, K., & Kastin, A. J. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7215 · Cited by 36
Self-citation
Feeding Peptides Interact in Several Ways with the Blood-Brain Barrier
Kastin, A. J., & Pan, W. (2003) · Current Pharmaceutical Design · doi:10.2174/1381612033455378 · Cited by 32
Self-citation
Separate endocytic pathways regulate IL-5 receptor internalization and signaling
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Novel peptide–peptide cooperation may transform feeding behavior
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Self-citation
Cerebral microvascular IL15 is a novel mediator of TNF action
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Self-citation

Research works printed but not linked: 6

[21]Pan W Xiang S Tu H Kastin AJ Dermietzel R Spray DC Nedergaard M In Blood-Brain Barrier Interfaces: From Ontogeny to Artificial Barriers 2006 247 64 Wiley-VCH Weinheim, Germany
[76]Yu Y Kastin AJ Pan W Reciprocal interactions of insulin and IGF-1 in receptor-mediated transport across the BBB. Endocrinol 2006 147 2611 5 16497794
[90]Tu H Kastin AJ Pan W CRH-R1 and CRH-R2 are both trafficking and signaling receptors for urocortin. Mol Endocrinol 2007 21 700 11 17170072
[135]Tu H Kastin AJ Pan W CRH-R1 and CRH-R2 are both trafficking and signaling receptors for urocortin. Mol Endocrinol 2007 21 700 11 17170072
[171]Tu H Kastin AJ Bjorbaek C Pan W Urocortin trafficking in cerebral microvessel endothelial cells. J Mol Neurosci 2007 31 171 82 17478891
[189]Barger PM Browning AC Garner AN Kelly DP p38 mitogen-activated protein kinase activates peroxisome proliferator-activated receptor alpha: a potential role in the cardiac metabolic stress response. J Biol Chem 2001 276 48 44495 501 11577087

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See all 241

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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