| First Author | Straccia M | Year | 2013 |
| Journal | Glia | Volume | 61 |
| Issue | 10 | Pages | 1607-19 |
| PubMed ID | 23893854 | Mgi Jnum | J:199563 |
| Mgi Id | MGI:5503233 | Doi | 10.1002/glia.22542 |
| Citation | Straccia M, et al. (2013) CCAAT/Enhancer binding protein beta regulates prostaglandin E synthase expression and prostaglandin E2 production in activated microglial cells. Glia 61(10):1607-19 |
| abstractText | 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 beta (C/EBPbeta) regulates the expression of prostaglandin synthesis enzymes in neuroinflammation. To this aim, the expression of these enzymes in wild-type and C/EBPbeta-null mice was analyzed in vitro and in vivo. In mixed glial cultures, lipopolysaccharide (LPS) +/- interferon gamma (IFN-gamma) induced C/EBPbeta binding to COX-2 and PTGES promoters. LPS +/- IFN-gamma-induced increases in PTGES expression and in PGE2 production in mixed glial and microglial cultures were abrogated in the absence of C/EBPbeta. Also, increased brain PTGES expression induced by systemic LPS administration was markedly reduced in C/EBPbeta-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/EBPbeta. These results demonstrate that C/EBPbeta regulates PTGES expression and PGE2 production by activated microglial cells in vitro and point to C/EBPbeta as a regulator of PTGES expression in vivo in the inflamed central nervous system. Altogether, these findings strengthen the proposed role of C/EBPbeta as a key player in the orchestration of neuroinflammatory gene response. GLIA 2013;61:1607-1619. |
