D-Mannose ameliorates DNCB-induced atopic dermatitis in mice and TNF-alpha-induced inflammation in human keratinocytes via mTOR/NF-kappa B pathway

D-mannose is a C-2 epimer of glucose, widely distributed in nature. Atopic dermatitis (AD) is a chronic in-flammatory disease characterized by repetitious itching. The present study aimed to explore the protective effect and the underlying mechanism of D-mannose against the development of atopic dermatitis. We tested the effect of D-mannose by establishing DNCB (2,4-dinitrochlorobenzene)-induced AD mice models in vivo and culturing keratinocytes (HaCaT and NHEK) in vitro. The skin lesion severity was evaluated by histochemical staining. Cytokine expression levels were measured by real-time PCR and ELISA assay. The expression of the mammalian target of rapamycin (mTOR)/ nuclear transcription factor kappa B (NF-kappa B)-signaling-related molecules were deter-mined by western blotting. Here, we found that topical supplementation of D-mannose remarkably attenuated skin lesions and recovered skin barrier function in AD mice model induced by DNCB. Furthermore, in vivo and in vitro experiments indicated that D-mannose inhibited tumor necrosis factor-alpha (TNF-alpha)-mediated increased expression of inflammatory cytokines. D-mannose also markedly downregulated TNF-alpha-stimulated activation of mTOR/NF-kappa B signaling pathway that was crucial for regulating the inflammatory condition. However, these effects were abolished by treatment with inhibitors of mTOR or NF-kappa B in HaCaT and NHEK. As far as we know, this is the first study uncovering the effective role of D-mannose via skin topical application. We found that D-mannose plays a regulatory role on inflammatory keratinocytes, suggesting its therapeutic utilization as a po-tential drug against atopic dermatitis.