Inhibitory effect of water-soluble chitosan on TNF-alpha and IL-8 secretion from HMC-1 cells

Mast cells are known to play an active role as effector cells in allergic inflammation and in diverse immunological and pathological processes. Activated mast cell-derived pro-inflammatory cytokines are important pathologic factors of progression of allergic inflammation. In this study, we investigated whether pro-inflammatory cytokines (TNF-alpha and IL-8) can be induced by calcium stimulation in HMC-1 cells, and high molecular weight water-soluble chitosan (WSC) can inhibit the production of these cytokines. We provided evidence that the secretion of TNF-alpha and IL-8 from HMC-1 cells was induced by Ca2+-ionophore A23187 or Ca2+-ATPase inhibitor TSG. Treatment of WSC (10 mug/ml) prior to stimulation with calcium agonists significantly blocked the secretion of TNF-alpha by 65.1% for A23187 and 87.7% for TSG. IL-8 secretion in response to A23187 or TSG was inhibited by 49.2% for A23187 and 34.1% for TSG, respectively, compared to absence of WSC. These results suggest that WSC has potential regulatory effects on allergic inflammatory diseases by down-modulating Ca2+-induced mast cell activation.