title: Beta-naphthoflavone disturbs astrocytic differentiation of C6 glioma cells by inhibiting autocrine interleukin-6.
abstract: Regulation of astrocyte differentiation is a key process in the development of the central nervous system (CNS), and disturbance of the differentiation can lead to brain system dysfunction. Here we show that beta-naphthoflavone (betaNF), an agonist of the aryl hydrocarbon receptor (AhR), disturbed the cAMP-induced astrocytic differentiation of C6 glioma by inhibiting autocrine interleukin-6 (IL-6). Treatment of cells with betaNF reduced the induction of an astrocyte marker glial fibrillary acidic protein (GFAP). This was caused by the inactivation of its upstream transcription factor signal transducer and activator of transcription 3 (STAT3) by betaNF. In addition, betaNF attenuated the induction of the IL-6 gene, which leads to the activation of STAT3. Most importantly, the inhibitory effect of betaNF on GFAP promoter activity was recovered by the addition of recombinant IL-6. Taken together, these results indicate that the inhibitory effect of betaNF on IL-6 induction suppresses STAT3 activation. These processes subsequently lead to the attenuation of GFAP induction.
authors.affiliation: Department of Public Health, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan. mt375@cam.ac.uk
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takanaga
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshitake
authors.forename: Emi
authors.initials: E
authors.lastname: Yatabe
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Manabu
authors.initials: M
authors.lastname: Kunimoto
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology*; D019898:Autocrine Communication / Q000187:drug effects*; D003994:Bucladesine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013806:Theophylline / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D019324:beta-Naphthoflavone / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D018336:Receptors, Aryl Hydrocarbon; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D019324:beta-Naphthoflavone; D003994:Bucladesine; D013806:Theophylline