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CCAAT/enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E2 production in activated microglial cells

, : CCAAT/enhancer binding protein β regulates prostaglandin E synthase expression and prostaglandin E2 production in activated microglial cells. Glia 61(10): 1607-1619

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.


PMID: 23893854

DOI: 10.1002/glia.22542

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