title: c-Jun is essential for the induction of Il-1β gene expression in in vitro activated Bergmann glial cells.
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.
authors.affiliation: Institut for Clinical Neurobiology, University of Würzburg, D-97078 Würzburg, Germany.
authors.forename: Lidia
authors.initials: L
authors.lastname: Albanito
authors.forename: Chandrakanth Edamakanti
authors.initials: CE
authors.lastname: Reddy
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Musti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018920:Coculture Techniques; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D016755:Proto-Oncogene Proteins c-jun / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D053583:Interleukin-1beta; D016755:Proto-Oncogene Proteins c-jun