Journal
NEUROSCIENCE LETTERS
Volume 321, Issue 1-2, Pages 105-109Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/S0304-3940(02)00066-6
Keywords
Alzheimer's disease; water-soluble chitosan; astrocyte; beta-amyloid; interleukin-1 beta; tumor necrosis factor-alpha; interieukin-6; inducible nitric-oxide synthase
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A chronic inflammatory response associated with beta-amyloid (Abeta) and interleukin-1beta (IL-1beta) is responsible for the pathology of Alzheimer's disease (AD). Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in AD. To investigate the biological effect of water-soluble chitosan (WSC), we examined cytotoxicity, production of pro-inflammatory cytokines and inducible nitric-oxide synthase (iNOS) on human astrocytoma cell line CCF-STTG1 stimulated with IL-1beta and Abeta fragment 25-35 (Abeta[25-35]). In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide colorimetric assay, WSC by itself had no effect on cell viability on human astrocytoma cells. The effects of WSC on tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were evaluated with enzyme-linked immunosorbent assay and Western blotting. The production of TNF-alpha and IL-6 was induced by IL-1beta and Abeta[25-35] and synergistically amplified by the co-stimulation of IL-1beta and AP[25-35]. The secretion and expression of pro-inflammatory cytokines, TNF-alpha and IL-6, was significantly inhibited by pretreatment with WSC in human astrocytoma cells. The expression of iNOS was induced by IL-1beta and Abeta[25-35] and was partially inhibited by treatment with WSC. We demonstrate the regulatory effects of WSC in human astrocytes for the first time and suggest the anti-inflammatory effect of WSC may reduce and delay AD pathologic events. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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