Selective induction of cAMP phosphodiesterase PDE4B2 expression in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) in Lewis rats is the most widely used animal model for multiple sclerosis. Cyclic adenosine monophosphate (cAMP) has been associated with neuroinflammation. The aim of this study was to investigate the possible involvement of different cAMP-specific phosphodiesterase (PDE) isoenzymes by analyzing their expression in the brain of EAE rats. We found in the brain of EAE animals that there was a dramatic increase in the mRNA expression levels of the PDE4B isozyme detected around blood vessels from the spinal cord to the upper midbrain. There was a single splicing form of the 4 splice variants that are known for PDE4B: PDE4B2, which showed increased expression levels. This overexpression is localized around the blood vessels and parenchyma in infiltrating T cells and macrophages/microglia. These results support the role played by the activation of the PDE4B2 gene in the neuroinflammatory process in EAE rats.
Reyes-Irisarri
Elisabet
E
Department of Neuropharmacology, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Cientificas (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain.
Sánchez
Antonio J
AJ
García-Merino
Juan Antonio
JA
Mengod
Guadalupe
G
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology*; D004790:Enzyme Induction; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew
D007527:Isoenzymes; D012333:RNA, Messenger; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D054708:Cyclic Nucleotide Phosphodiesterases, Type 7