TNFalpha transport across the blood-brain barrier is abolished in receptor knockout mice

Experimental Neurology
Weihong Pan, Abba J Kastin

Abstract

The presence of transport systems at the blood-brain barrier (BBB) enables some cytokines in blood to reach specific targets in the brain and spinal cord. The "transporters" function in a way different from conventional receptors, in that cytokines are chaperoned from blood to the CNS rather than being degraded in the specialized endothelial cells composing the BBB. Here we present the first study to determine whether the transporter for tumor necrosis factor-alpha (TNFalpha) is identical to its receptors. Three types of TNFalpha receptor knockout mice were used, and the influx of (125)I-TNFalpha from blood to brain and blood to spinal cord was measured. In either p55 or p75 receptor knockout mice, the influx of (125)I-TNFalpha was significantly, but not completely, decreased in spinal cord, whereas the decrease in brain was not statistically significant. This indicates that both receptors are partially involved in the transport of TNFalpha across the BBB but that neither receptor is the sole transporter. By contrast, in double knockout mice lacking both p55 and p75 receptors, the entry of (125)I-TNFalpha into brain and spinal cord was completely abolished. Therefore, both receptors are necessary for transporting TNFalpha acros...Continue Reading

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Citations

Nov 6, 2007·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Chuanhui YuWeihong Pan
Dec 18, 2008·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Chuanhui YuWeihong Pan
Jun 1, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Weihong PanAbba J Kastin
Jan 18, 2012·Neuroimmunomodulation·Michelle A EricksonWilliam A Banks
May 19, 2012·Journal of Neuroinflammation·Elisa GreggioLuigi Bubacco
May 24, 2011·Parkinson's Disease·Mei Liu, Guoying Bing
Jun 5, 2013·Proceedings of the National Academy of Sciences of the United States of America·Guang YangWen-Biao Gan
Jan 1, 2003·Journal of Neuroimmunology·Weihong PanAbba J Kastin
Sep 18, 2007·Journal of Molecular Neuroscience : MN·Chuanhui YuWeihong Pan
Feb 14, 2013·Journal of Pharmacokinetics and Pharmacodynamics·Scott G Summerfield, Kelly C Dong
Jun 1, 2012·Drug Delivery and Translational Research·William A Banks
Jun 17, 2006·Journal of Drug Targeting·Mathew W Smith, Mark Gumbleton
Aug 6, 2010·Brain Research Reviews·Filipa Lourenço CardosoMaria Alexandra Brito
Oct 5, 2007·Progress in Neurobiology·Weihong Pan, Abba J Kastin
Jul 3, 2007·Brain, Behavior, and Immunity·Ning Quan, William A Banks
Jun 2, 2007·Peptides·Weihong Pan, Abba J Kastin
Apr 20, 2004·European Journal of Pharmacology·William A Banks
Sep 16, 2006·Experimental Neurology·Chuanhui YuWeihong Pan
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Aug 12, 2009·Neurobiology of Disease·N Joan AbbottDavid J Begley
Aug 12, 2009·Neurobiology of Disease·William A Banks, Michelle A Erickson
Aug 7, 2004·Brain Research. Brain Research Reviews·Weihong Pan, Abba J Kastin
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Yun DongUlrich L M Eisel
Feb 27, 2017·Neurobiology of Disease·Astrid WeilerStefanie Schirmeier
Dec 8, 2016·Physiology & Behavior·Stephen C WoodsDenovan P Begg
Jul 26, 2018·The Journal of Physiology·Elizabeth M RheaWilliam A Banks
Jul 11, 2007·Journal of Cellular Physiology·Hong TuWeihong Pan
Sep 1, 2007·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Weihong PanAbba J Kastin
Sep 2, 2009·Journal of Neurochemistry·Weihong PanAbba J Kastin
Aug 24, 2005·The European Journal of Neuroscience·Florence MillerValérie Buée-Scherrer

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