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Glia. 2007 Jan 15;55(2):178-88.

Upregulation of CCAAT/enhancer binding protein beta in activated astrocytes and microglia.

Author information

1
Department of Pharmacology and Toxicology, IIBB-CSIC, IDIBAPS, E-08036 Barcelona, Spain.

Abstract

The transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) regulates the expression of key genes in inflammation but little is known about the involvement of C/EBPbeta in glial activation. In this report, we have studied the patterns of astroglial and microglial C/EBPbeta expression in primary mouse cortical cultures. We show that both astrocytes and microglia express C/EBPbeta in untreated mixed glial cultures. C/EBPbeta is upregulated when glial activation is induced by lipopolysaccharide (LPS). The LPS-induced upregulation of glial C/EBPbeta is rapid (2 h at mRNA level, 4 h at protein level). It is elicited by low concentrations of LPS (almost maximal effect at 1 ng/mL) and it is reversed by the protein synthesis inhibitor cycloheximide. C/EBPbeta nuclear levels increase both in astrocytes and microglia after LPS treatment, and the response is more marked in microglia. The LPS-induced increase in microglial C/EBPbeta is prevented by coadministration of the MAP kinase inhibitors SB203580 (p38 inhibitor) + SP600125 (JNK inhibitor) or SB203580 + U0126 (ERK inhibitor). Systemic injection of LPS also increases brain nuclear levels of C/EBPbeta as shown by Western blot, and this increase is localized in microglial cells as shown by double immunofluorescence, in the first report to our knowledge of C/EBPbeta expression in activated glial cells in vivo. These findings support a role for C/EBPbeta in the activation of astrocytes and, particularly, microglia. Given the nature of the C/EBPbeta-regulated genes, we hypothesize that this factor participates in neurotoxic effects associated with glial activation.

PMID:
17078024
DOI:
10.1002/glia.20446
[Indexed for MEDLINE]

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