title: CCAAT/enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E2 production in activated microglial cells.
abstract: The eicosanoid prostaglandin E2 (PGE2 ) plays important roles in neuroinflammation and it is produced by the sequential action of the enzymes cyclooxygenase-2 (COX-2) and prostaglandin E synthase (PTGES). The expression of both enzymes and the production of PGE2 are increased in neuroinflammation. The objective of this study was to elucidate whether the transcription factor CCAAT/enhancer binding protein β (C/EBPβ) regulates the expression of prostaglandin synthesis enzymes in neuroinflammation. To this aim, the expression of these enzymes in wild-type and C/EBPβ-null mice was analyzed in vitro and in vivo. In mixed glial cultures, lipopolysaccharide (LPS) ± interferon γ (IFN-γ) induced C/EBPβ binding to COX-2 and PTGES promoters. LPS ± IFN-γ-induced increases in PTGES expression and in PGE2 production in mixed glial and microglial cultures were abrogated in the absence of C/EBPβ. Also, increased brain PTGES expression induced by systemic LPS administration was markedly reduced in C/EBPβ-null mice. In contrast to PTGES, the induction of COX-2 expression in vitro or in vivo was not markedly affected by the absence of C/EBPβ. These results demonstrate that C/EBPβ regulates PTGES expression and PGE2 production by activated microglial cells in vitro and point to C/EBPβ as a regulator of PTGES expression in vivo in the inflamed central nervous system. Altogether, these findings strengthen the proposed role of C/EBPβ as a key player in the orchestration of neuroinflammatory gene response.
authors.affiliation: Biochemistry and Molecular Biology Unit, School of Medicine, University of Barcelona, IDIBAPS, Barcelona, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Straccia
authors.forename: Guido
authors.initials: G
authors.lastname: Dentesano
authors.forename: Tony
authors.initials: T
authors.lastname: Valente
authors.forename: Marta
authors.initials: M
authors.lastname: Pulido-Salgado
authors.forename: Carme
authors.initials: C
authors.lastname: Solà
authors.forename: Josep
authors.initials: J
authors.lastname: Saura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D023081:CCAAT-Binding Factor / Q000172:deficiency / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D000071876:Prostaglandin-E Synthases; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; D007041:Hypoxanthine Phosphoribosyltransferase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone
keywords: C/EBP; COX-2; PTGES; glial activation; microglia; neuroinflammation; prostaglandin E 2