Chitin and
chitosan have versatile anti-
tumor, anti-fungal, and antimicrobial biological properties. Oral intakes and
intranasal administration of
chitin attenuated
allergen-induced airway
inflammation in sensitized mice, which may be due to its Th1 adjuvant properties. However, their mechanism of action is not entirely clear. In this report, we demonstrate that water-soluble
chitosan (WSC) has specific immunomodulatory effects on dust mite
allergen Dermatophagoides farinae (Der f)-stimulated, monocyte-derived macrophages (MDM). These effects include polarizing the
cytokine balance towards Th1
cytokines, decreasing the production of the inflammatory
cytokines IL-6 and
TNF-alpha, down-regulating CD44 and
TLR4 receptor expression, and inhibiting T cell proliferation. Scanning electron microscope (SEM) examination found that WSC reduced the rate of pseudopodia formation in Der f-stimulated MDM from allergic
asthma patients. The effect of WSC on
allergen-stimulated MDM may be mediated via inhibition of PKCzeta phosphorylation and
NF-kappaB pathway activation. In a murine model of
asthma, we found that intranasal application of WSC attenuates Der f-induced
lung inflammation by reducing infiltration of inflammatory cells, epithelial damage, and goblet cell
hyperplasia and markedly decreasing production of Arg I, iNOs, and
thymic stromal lymphopoietin (TSLP) in the bronchial epithelium. Therefore, we believe that WSC may provide a new therapeutic modality for allergic
asthma.