Chotosan Enhances Macrophage Colony-Stimulating Factor mRNA Expression in the Ischemic Rat Brain and C6Bu-1 Glioma Cells

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Author(s)

    • Obi Ryosuke OBI Ryosuke
    • Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
    • OBI Nobuko
    • Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
    • HORI Hitomi
    • Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama
    • MURAKAMI Yukihisa
    • Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama
    • GOTO Hirozo
    • Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
    • SHIMADA Yutaka
    • Department of Japanese Oriental Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama
    • OCHIAI Hiroshi
    • Department of Human Science, Faculty of Medicine, University of Toyama
    • MATSUMOTO Kinzo
    • Division of Medicinal Pharmacology, Institute of Natural Medicine, University of Toyama

Abstract

Macrophage colony stimulating factor (M-CSF) is a cytokine which has been recently reported to have a neuroprotective effect on ischemic rat brain. In this study, we investigated the effect of chotosan, an oriental medicine, which has been clinically demonstrated to be effective for the treatment of vascular dementia, on M-CSF gene expression in rats with permanent occlusion of bilateral common carotid arteries (P2VO) <i>in viv</i>o and in a C6Bu-1 glioma cell line <i>in vitro</i>. The expression level of M-CSF mRNA in the cerebral cortices of P2VO rats was significantly higher than that in the cerebral cortices of sham-operated animals. Repeated treatment of P2VO rats with chotosan (75 mg/kg per day) for 4 d after P2VO significantly increased the expression level of M-CSF mRNA in the cortex but it had no effect on the expression of β-actin, granulocyte colony stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor (GM-CSF) mRNAs. Moreover, the present<i> in vitro </i>studies revealed that chotosan treatment (10—100 μg/ml) of C6Bu-1 glioma cells dose-dependently enhanced M-CSF mRNA expression without affecting the expression of G-CSF, GM-CSF, and inducible nitric oxide synthase mRNAs. The effect of chotosan was reversed by Ro 31-8220 (1 μ<small>M</small>), a selective protein kinase C (PKC) inhibitor, but not by H-89 (10 μ<small>M</small>), a selective protein kinase A (PKA) inhibitor. These findings suggest that the upregulatory effect of chotosan on M-CSF mRNA expression involves PKC and may play an important role in the anti-vascular dementia action of this formula.

Journal

  • Biological and Pharmaceutical Bulletin

    Biological and Pharmaceutical Bulletin 30(12), 2250-2256, 2007-12-01

    The Pharmaceutical Society of Japan

References:  41

Codes

  • NII Article ID (NAID)
    110006546420
  • NII NACSIS-CAT ID (NCID)
    AA10885497
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09186158
  • NDL Article ID
    9274199
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-V41
  • Data Source
    CJP  NDL  NII-ELS  J-STAGE 
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