Inhibitory effect of high molecular weight water-soluble chitosan on hypoxia-induced inflammatory cytokine production

Abstract

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 IC50 values of 0.77, 0.88, and 2.5 μg/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)-κB. In conclusion, these results suggest that WSC is an inhibitor of NF-κS under hypoxic conditions, which might explain its beneficial effect in the treatment of hypoxia-induced inflammatory diseases.