The prevention of TNF-α/IFN-γ mixture-induced inflammation in human keratinocyte and atopic dermatitis-like skin lesions in Nc/Nga mice by mineral-balanced deep sea water

Biomed Pharmacother. 2018 Jan:97:1331-1340. doi: 10.1016/j.biopha.2017.11.056. Epub 2017 Nov 14.

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by environmental and chemical allergens. Despite the complexity of its pathogenesis, many investigations have shown that substances having anti-inflammatory activities alleviated the pathology of AD. Here, we evaluated the effects of mineral-balanced deep sea water (DSW) on AD-like skin damage in both in vitro and in vivo. The results showed that mineral-balanced DSW regressed inflammatory chemokines, such as macrophage-derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC) and regulated on activation, normal T-cell expressed and secreted (RANTES), and cytokines, interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression in HaCaT immortal human keratinocyte treated with tumor necrosis factor (TNF)-α/ interferon (IFN)-γ mixture. Furthermore, increased cyclooxygenase (COX)-2 protein expressions were also reversed, filaggrin gene expression was enhanced and decreased involucrin transcriptions was recovered by mineral-balanced DSW in TNF-α/IFN-γ mixture-treated HaCaT human keratinocyte. Moreover, we revealed that the inhibitory effects of mineral-balanced DSW were mediated with the suppression of signal transducer and activator of transcription (STAT) 1 phosphorylation. In animal experiments, we showed that hardness 2000 of mineral-balanced DSW decreased the serum levels of IgE, IL-4, and histamine, and alleviated the severity score and numbers of scratching in dinitrochlorobezene (DNCB)-treated Nc/Nga mice. Furthermore, increased epidermal thickness and mast cell infiltration by DNCB treatment were reversed by the application of hardness 2000 mineral-balanced DSW. Taken together, the present investigation indicates that mineral-balanced DSW is a potent substance with anti-atopic dermatitis activity.

Keywords: Atopic dermatitis; Chemokines; Inflammation; Keratinocyte; Mineral-balanced deep sea water; Nc/Nga mice.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Chemokines / metabolism
  • Cytokines / metabolism
  • Dermatitis, Atopic / pathology
  • Dermatitis, Atopic / prevention & control*
  • Disease Models, Animal
  • Filaggrin Proteins
  • Gene Expression Regulation
  • Humans
  • Inflammation / pathology
  • Inflammation / prevention & control*
  • Interferon-gamma / administration & dosage
  • Interferon-gamma / metabolism
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Male
  • Mast Cells / metabolism
  • Mice
  • Mineral Waters / administration & dosage*
  • Seawater / chemistry
  • Tumor Necrosis Factor-alpha / administration & dosage
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Chemokines
  • Cytokines
  • FLG protein, human
  • Filaggrin Proteins
  • Mineral Waters
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma