D-Mannose ameliorates DNCB-induced atopic dermatitis in mice and TNF-α-induced inflammation in human keratinocytes via mTOR/NF-κB pathway.
D-Mannose ameliorates DNCB-induced atopic dermatitis in mice and TNF-α-induced inflammation in human keratinocytes via mTOR/NF-κB pathway.
复制标题
d -甘露糖通过mTOR/NF-κB通路改善dncb诱导的小鼠特应性皮炎和TNF-α-诱导的人角质形成细胞炎症。
DOI：
10.1016/j.intimp.2022.109378
复制
发表时间：
2022-10
影响因子：
5.6
通讯作者：
Jialiang Luo;Yao Li;Yumeng Zhai;Yao Liu;Junxiang Zeng;Di Wang;Lei Li;Zhengyumeng Zhu;
中科院分区：
文献类型：
--
作者：
Jialiang Luo;Yao Li;Yumeng Zhai;Yao Liu;Junxiang Zeng;Di Wang;Lei Li;Zhengyumeng Zhu;
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 modelsin vivoand 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 vivoandin vitroexperiments 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.
