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

• Published in: International immunopharmacology Vol. 113; p. 109378
• Main Authors: Luo, Jialiang, Li, Yao, Zhai, Yumeng, Liu, Yao, Zeng, Junxiang, Wang, Di, Li, Lei, Zhu, Zhengyumeng, Chang, Bo, Deng, Fan, Zhang, Jing, Zhou, Jia, Sun, Ledong
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.12.2022
• Subjects: Atopic dermatitis; Keratinocytes; Mannose; mTOR/NF-κB signaling; AD; H&E; IgE; Keratinocytes; DNCB; Mannose; EPX; DMEM; NF-κB; TNF-α; Atopic dermatitis; FBS; mTOR; mTOR/NF-κB signaling; DC
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2022.109378

•Topical application of mannose attenuates DNCB-induced atopic dermatitis.•Mannose regulates inflammatory condition and recovers skin barrier function.•Mannose treatment inhibits mTOR/NF-κB signaling in inflamed keratinocytes. D-mannose is a C-2 epimer of glucose, widely distributed in nature. Atopic dermatitis (AD) is a chronic inflammatory 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 κB (NF-κB)-signaling-related molecules were determined 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-α (TNF-α)-mediated increased expression of inflammatory cytokines. D-mannose also markedly downregulated TNF-α-stimulated activation of mTOR/NF-κB signaling pathway that was crucial for regulating the inflammatory condition. However, these effects were abolished by treatment with inhibitors of mTOR or NF-κB 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 potential drug against atopic dermatitis.