2. Academic Validation
  3. 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

  • Int Immunopharmacol. 2022 Dec;113(Pt A):109378. doi: 10.1016/j.intimp.2022.109378.
Jialiang Luo 1,  Yao Li 2,  Yumeng Zhai 3,  Yao Liu 3,  Junxiang Zeng 4,  Di Wang 5,  Lei Li 6,  Zhengyumeng Zhu 6,  Bo Chang 7,  Fan Deng 6,  Jing Zhang 7,  Jia Zhou 8,  Ledong Sun 9
Affiliations

Affiliations

  • 1 Department of Dermatology, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
  • 2 Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, China.
  • 3 Department of Dermatology, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 4 Department of Bioinformation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
  • 5 Department of Dermatology, Dermatology Hospital of Southern Medical University, Southern Medical University, Guangzhou, Guangdong, China.
  • 6 Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
  • 7 Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
  • 8 Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: [email protected].
  • 9 Department of Dermatology, the Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: [email protected].
PMID: 36327873 DOI: 10.1016/j.intimp.2022.109378
Abstract

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.

Keywords

Atopic dermatitis; Keratinocytes; Mannose; mTOR/NF-κB signaling.

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