C-Jun is essential for the induction of Il-1β gene expression in in vitro activated Bergmann glial cells

Lidia Albanito, Chandrakanth Edamakanti Reddy, Anna Maria Musti*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

In the central nervous system (CNS), the c-Jun transcription factor has been mainly studied in neuronal cells and coupled to apoptotic and regenerative pathways following brain injury. Besides, several studies have shown a transcriptional role of c-Jun in activated cortical and spinal astrocytes. In contrast, little is known about c-Jun expression and transactivation in Bergmann glial (BG) cells, the radial cerebellar astrocytes playing crucial roles in cerebellar development and physiology. Here, we used neuronal/glial cerebellar cultures from neonatal mice to assess putative functions of c-Jun in BG cells. By performing double immunocytochemical staining of c-Jun and two BG specific markers, S100 and glutamate aspartate transporter (GLAST), we show that c-Jun was highly expressed in radial glial cells derived from Bergmann glia. Bergmann glia-derived cells expressed toll-like receptor 4 and treatment with bacterial lipopolysaccharide (LPS)-induced c-Jun phosphorylation at serine 63, a hallmark of c-Jun transactivation, exclusively in BG cells. Moreover, LPS-induced IL-1β expression and inhibition of c-Jun N-terminal kinase (JNK) activity abolished both c-Jun phosphorylation and the increase of IL-1β mRNA. Notably, LPS failed to induce IL-1β mRNA in neuronal/glial cerebellar cultures generated from conditional knockout mice lacking c-Jun expression in the CNS, indicating the essential role of c-Jun in astroglial-specific induction of IL-1β. Immunohistochemical analyses of c-Jun-expressing cells in the early postnatal cerebellum confirmed in vivo the expression of c-Jun in BG cells and uncovered a dynamic expression of c-Jun during the formation of the BG monolayer. Altogether, our finding underlines a putative role of c-Jun in astroglia-mediated neuroinflammatory dysfunctions of the cerebellum.

Original languageEnglish (US)
Pages (from-to)1879-1890
Number of pages12
JournalGlia
Volume59
Issue number12
DOIs
StatePublished - Dec 1 2011

Keywords

  • Bergmann glia
  • C-Jun
  • Cerebellum
  • Glial activation
  • Il-1β
  • TLR4

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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