c-Jun Is Essential for the Induction of Il-1β Gene Expression in In Vitro Activated Bergmann Glial Cells

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-1 beta expression and inhibition of c-Jun N-terminal kinase (JNK) activity abolished both c-Jun phosphorylation and the increase of IL-1 beta mRNA. Notably, LPS failed to induce IL-1 beta 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-1 beta. 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 neuroinflammatorydysfunctions of the cerebellum. (C) Wiley-Liss, Inc.