Refined Deep-Sea Water Suppresses Inflammatory Responses via the MAPK/AP-1 and NF-κB Signaling Pathway in LPS-Treated RAW 264.7 Macrophage Cells

Int J Mol Sci. 2017 Oct 31;18(11):2282. doi: 10.3390/ijms18112282.

Abstract

Atopic dermatitis (AD) is a type of inflammatory skin disease caused by genetics, immune system dysfunction, and environmental stresses. It is, however, still considered to be a refractory disease. Macrophages are inflammatory immune cells that infiltrate the skin and induce inflammation. We investigated the effect of refined deep-sea water (RDSW) on lipopolysaccharide (LPS)-induced inflammatory response in RAW 264.7 macrophage cells. The results showed that RDSW suppressed the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Furthermore, nitric oxide, a product of iNOS, and prostaglandin (PG) D₂ and PGE₂, products of COX-2, were significantly inhibited by RDSW in a hardness-dependent manner. Moreover, we found that RDSW reversed the release of histamines and regressed the mRNA expressions and production of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10, and vascular endothelial growth factor, in a hardness-dependent manner. We also found that the suppressive effect of RDSW on LPS-induced inflammatory responses was regulated by the inhibition of NF-κB nuclear translocation, and ERK 1/2 and JNK 1/2 mediated the suppression of c-Jun and c-Fos expressions. In conclusion, the present investigation suggests the possibility that RDSW may be used to treat and/or prevent inflammatory diseases, including AD.

Keywords: RAW 264.7 macrophage cells; atopic dermatitis; inflammation; lipopolysaccharide; refined deep-sea water.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Histamine / metabolism
  • JNK Mitogen-Activated Protein Kinases / genetics
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Prostaglandins / metabolism
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Seawater*
  • Transcription Factor AP-1 / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • NF-kappa B
  • Prostaglandins
  • Proto-Oncogene Proteins c-fos
  • Transcription Factor AP-1
  • Histamine
  • Nitric Oxide Synthase Type II
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3