ICAM-1 upregulation in the spinal cords of PLSJL mice with experimental allergic encephalomyelitis is dependent upon TNF-alpha production triggered by the loss of blood-brain barrier integrity.
Urate (UA) selectively scavenges peroxynitrite-dependent radicals and suppresses CNS inflammation through effects that are manifested at the blood-brain barrier (BBB). ICAM-1 upregulation in the spinal cord tissues of myelin basic protein (MBP) immunized mice is selectively inhibited by UA treatment. In contrast, the expression of ICAM-1 and other adhesion molecules by circulating cells is unchanged. Moreover, TNF-alpha expression in the CNS tissues of MBP-immunized mice is suppressed by UA treatment but TNF-alpha-induced ICAM-1 expression on neurovascular endothelial cells is not. Therefore the effect of UA on ICAM-1 upregulation in the CNS tissues is likely due to its known contribution to the maintenance of BBB integrity in MBP-immunized mice which in turn inhibits cell invasion into the CNS and prevents TNF-alpha production in CNS tissues.
Scott
Gwen S
GS
Department of Microbiology and Immunology, Thomas Jefferson University, JAH 454, 1020 Locust Street, Philadelphia, PA 19107, USA.
Kean
Rhonda B
RB
Fabis
Marzena J
MJ
Mikheeva
Tatiana
T
Brimer
Christine M
CM
Phares
Timothy W
TW
Spitsin
Sergei V
SV
Hooper
D Craig
DC
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D030421:Peroxynitrous Acid / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D014527:Uric Acid / Q000494:pharmacology* / Q000627:therapeutic use
D016166:Free Radical Scavengers; D005609:Free Radicals; D004676:Myelin Basic Protein; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D030421:Peroxynitrous Acid; D014527:Uric Acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse