Open AccessNeuroinflammation Activates Mdr1b Efflux Transport Through NFκB: Promoter Analysis in BBB Endothelia
Author(s) -
Cong Yu,
George Argyropoulos,
Yan Zhang,
Abba J. Kastin,
Hung Hsuchou,
Weihong Pan
Publication year - 2008
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000185558
Subject(s) - downregulation and upregulation , chromatin immunoprecipitation , microbiology and biotechnology , p glycoprotein , proinflammatory cytokine , transcription factor , efflux , chemistry , biology , electrophoretic mobility shift assay , promoter , gene expression , inflammation , gene , biochemistry , multiple drug resistance , immunology , antibiotics
Although it is known that drug delivery across the blood-brain barrier (BBB) may be hampered by efflux transport activity of the multidrug resistance (mdr) gene product P-glycoprotein, it is not clear how inflammation regulates efflux transporters. In rat brain endothelial (RBE4) cells of BBB origin, the proinflammatory cytokine TNF mainly induced transcriptional upregulation of mdr1b, and to a lesser extent mdr1a, resulting in greater efflux of the substrates. This study further determines the mechanisms by which TNF activates mdr1b promoter activity.