We have already shown that glucosamine downregulates the overproduction of IgE and Th2 cytokines in an NC/Nga mice model of Df-induced AD, a major Th2-dominant disease [16]. In addition, Th2-specific chemokines, TARC and eotaxin, have GSK2126458 cost been reported

to be highly expressed in the NC/Nag mice [30]. A previous report showed that tacrolimus (FK-506) markedly inhibited Df-induced expression of TARC and eotaxin [31]. The present study of immune responses clearly shows that IgE, Th2 cytokine (IL-5 and IL-13) and Th2 chemokines (TARC and eotaxin) in combination treatment with glucosamine plus tacrolimus (FK-506) were significantly lower than in the single-modality treatment with either alone. These results suggest that the improvement in Mdm2 antagonist clinical symptoms by combination treatment of glucosamine plus tacrolimus (FK-506) against therapeutic effects of Df-induced NC/Nga mice might be mediated, at least in part, by its inhibitory effect on IgE, Th2-mediated cytokine and chemokines. In fact, the correlation between the elevation of serum levels of total IgE, the production of Th2 cytokine and chemokines has been reported [30, 32]. In this study,

immunohistochemical analysis showed that treatment with glucosamine plus tacrolimus (FK-506) led to a higher decrease in the CD3+ T and CLA+ cell numbers compared to controls. Skin-homing T cells expressing CLA are important in the pathogenesis of AD [27]. In patients with AD, there is a significant increase in the number of circulating CLA+ cells, which

have an augmented capability to produce IL-4 and IL-13 compared to the cells from non-affected individuals [28]. It has been reported that cyclosporine treatment significantly reduced the percentages of CD3+ T cells and CLA+ cells in children with severe AD [33]. These results imply that CD3+ T cells and CLA+ cells may be important in the pathogenesis of AD and in the mechanism of action of this combination treatment. Current studies Dynein suggest that a single type of immunosuppressive therapy may be able to deal with all facets in the treatment of AD. However, a rational combination of synergistic therapy could provide a successful clinical approach to AD. An important finding in this study showed synergistic efficacy of combination therapy with glucosamine plus tacrolimus (FK-506) in Df-induced NC/Nga mice. In conclusion, our findings indicated that this combined immunosuppressive therapy was more efficacious than monotherapy in reducing IgE, Th2 cytokine levels and Th2 chemokine expression and in inhibiting inflammatory cells and CLA+ cell infiltration, and these findings correlated with the observed clinical symptoms. These findings have important implications for the design of therapeutic strategies aimed at AD treatment.