Rolipram impairs NF-kappaB activity and MMP-9 expression in experimental autoimmune encephalomyelitis.
Rolipram suppresses experimental autoimmune encephalomyelitis (EAE) and diminishes cell infiltration of the central nervous system (CNS). In Lewis rats with EAE, rolipram reduced matrix metalloproteinase-9 (MMP-9) gene expression in lymph node cells (LNCs) and spinal cord, decreased basal levels of nuclear (p50/p65) NF-kappaB in LNCs from treated rats, and impaired CD3 mediated NF-kappaB translocation. Rolipram reduced the luciferase activity directed by the NF-kappaB binding site of the MMP-9 gene in lymphocytes. It also diminished NF-kappaB activity and the ability of a myelin basic protein (MBP) specific cell line to migrate across artificial basement membranes. IL-2 induced MMP-9 proteolytic activity was only slightly reduced indicating that additional factors contribute to inhibit cell migration mediated by rolipram.
Sánchez
Antonio J
AJ
Neuroimmunology Unit, Universidad Autónoma de Madrid, Hospital Puerta de Hierro, San Martín de Porres 4, 28035, Madrid, Spain.
Puerta
Carmen
C
Ballester
Sara
S
González
Paz
P
Arriaga
Angel
A
García-Merino
Antonio
A
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D008156:Luciferases / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008214:Lymphocytes / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D004676:Myelin Basic Protein / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020889:Rolipram / Q000008:administration & dosage*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014162:Transfection / Q000379:methods
D004676:Myelin Basic Protein; D016328:NF-kappa B; D010726:Phosphodiesterase Inhibitors; D012333:RNA, Messenger; D008156:Luciferases; D020780:Matrix Metalloproteinase 9; D020889:Rolipram