Inhibitory Effect of High Molecular Weight Water-Soluble Chitosan on Hypoxia-Induced Inflammatory Cytokine Production

概要

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Chitosan is widely used to treat patients with hypoxia-induced diseases such as ischemia, neuronal death, cerebral stroke, and cerebral infarction. Using the ELISA method, we examined the effect of high molecular weight water-soluble chitosan (WSC) on inflammatory cytokine production in the desferrioxamine (DFX, known to mimic hypoxia)-stimulated human mast cell line HMC-1. DFX significantly increased interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α production compared with the control in a time-dependent manner (p<0.05), but did not affect IL-1α production and mRNA expression. The increase in IL-6, IL-8, and TNF-α levels was significantly inhibited by WSC in a dose-dependent manner with IC_<50> values of 0.77, 0.88, and 2.5/lg/ml, respectively. The maximal inhibition rate of IL-6, IL-8, and TNF-α production by WSC was 64±9.7%, 80±9.4% and 54±4.5%, respectively. In addition, WSC inhibited DFX-induced activation of nuclear factor (NF)-_KB. In conclusion, these results suggest that WSC is an inhibitor of NF-_KB under hypoxic conditions, which might explain its beneficial effect in the treatment of hypoxia-induced inflammatory diseases.
社団法人日本薬学会の論文
2003-05-01