008 and P = 0.011, respectively) and the control group (P = 0.001). No difference, however, was observed in IFN-γ production among all four groups (data not shown). ABT263 Cutaneous lymphocyte antigen is highly expressed on skin-infiltrating T cells in inflammatory skin diseases, including allergic contact dermatitis and atopic dermatitis [27]. The expressions of peripheral blood CD3+ CLA+ T cells were significantly increased in children with AD compared with those

in control subjects [28]. We found that the infiltration of Df-induced CLA+ and CD3+ T cells (coloured green with cell surface) in NC/Nga mice was inhibited by combination therapy of glucosamine plus tacrolimus (FK-506) (Fig. 5A,B). In addition, there was no significant difference between the combination group and normal (no dermatitis) group. Atopic dermatitis has this website been treated by the regular use of corticosteroids, which is not a perfect treatment because sufficient results cannot be provided in a number of cases as a result

of adverse events such as steroid-induced skin atrophy. Therefore, identified combinations of immunosuppressive agents are expected to be among the important future strategies for improved treatment of AD. It has been reported that the use of combinations of immunosuppressive agents may be more effective than single-modality treatment with either agent. In this study, we found that combination therapy with immunosuppressive agent glucosamine plus tacrolimus (FK-506) has a synergistic effect on Df-induced atopic dermatitis-like skin lesions in NC/Nga mice. For instance, combination treatment with glucosamine plus tacrolimus (FK-506) improved the severity of the dermatitis with reduction

in inflammatory cellular infiltrate, such as mast cells and eosinophils. For each parameter, we have repeated the experiment once using the same number of animals per group and found a similar type of profile, indicating that the results are reproducible (data not shown). These results indicated that combination therapy suppressed the development of Df-induced dermatitis, probably by controlling various inflammatory cells including mast cells and eosinophils. Because Th2 cytokines induce proliferation and activation Tangeritin of mast cells as well as eosinophils in the skin, massive infiltration of mast cells and eosinophils would be expected in Df-induced NC/Nga mice, as previously reported [24]. Th2 cytokines are considered to play a major role in the pathogenesis of AD [5]. In fact, Th2 immune responses mediated by IL-4, IL-5 and IL-13 are critical in the pathogenesis of AD [9], because the upregulation of IgE production, one of the major causes of atopic inflammation, has been extensively studied with Th2 cytokines, IL-5 and IL-13. Moreover, Th2 cell numbers are increased in lesional tissue of patients who suffer from patients with AD frequently show elevated IgE levels in response to many kinds of allergens, including mite antigen [29].