β‐Naphthoflavone disturbs astrocytic differentiation of C6 glioma cells by inhibiting autocrine interleukin‐6

• Published in: Journal of neurochemistry 2004-08, Vol.90 (3), p.750-757
• Main Authors: Takanaga, Hiromi, Yoshitake, Tomoko, Yatabe, Emi, Hara, Shuntaro, Kunimoto, Manabu
• Format: Article
• Language: English
• Subjects: Animals; aryl hydrocarbon receptor; astrocyte; Astrocytes - cytology; Autocrine Communication - drug effects; beta-Naphthoflavone - pharmacology; Biological and medical sciences; Bucladesine - pharmacology; Cell Differentiation - drug effects; Cell Line, Tumor; differentiation; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Glial Fibrillary Acidic Protein - genetics; Glial Fibrillary Acidic Protein - metabolism; Glioma - drug therapy; Glioma - metabolism; Interleukin-6 - metabolism; interleukin‐6; Isolated neuron and nerve. Neuroglia; Rats; Receptors, Aryl Hydrocarbon - agonists; Signal Transduction - drug effects; Signal Transduction - genetics; STAT3; STAT3 Transcription Factor; Theophylline - pharmacology; Trans-Activators - drug effects; Trans-Activators - metabolism; Vertebrates: nervous system and sense organs; β‐naphthoflavone
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2004.02681.x

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 β‐naphthoflavone (βNF), 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 βNF 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 βNF. In addition, βNF attenuated the induction of the IL‐6 gene, which leads to the activation of STAT3. Most importantly, the inhibitory effect of βNF on GFAP promoter activity was recovered by the addition of recombinant IL‐6. Taken together, these results indicate that the inhibitory effect of βNF on IL‐6 induction suppresses STAT3 activation. These processes subsequently lead to the attenuation of GFAP induction.