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Vitamin D₃ derivatives increase soluble CD14 release through ERK1/2 activation and decrease IL-8 production in

Mayumi Hidaka1, Ichiro Wakabayashi, Yuji Takeda

  • 1Department of Life Sciences, Faculty of Pharmacy, Yasuda Women's University, 6-13-1 Yasuhigashi, Asaminami-ku, Hiroshima 731-0153, Japan; Department of Environmental and Preventive Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.

European Journal of Pharmacology
|September 25, 2013
PubMed
Summary
This summary is machine-generated.

Vitamin D3 derivatives enhance the release of soluble CD14 (sCD14), an anti-inflammatory molecule, by activating the ERK1/2 pathway. This process reduces Interleukin-8 (IL-8) production, offering a potential therapeutic strategy for intestinal inflammation.

Keywords:
Extracellular signal-regulated kinase 1/2Interleukin-8Soluble form CD14Vitamin D(3)

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Innate immune system dysfunction is linked to intestinal inflammation.
  • Vitamin D3 is a known immune regulator with anti-inflammatory properties.

Purpose of the Study:

  • To investigate the in vitro effects of vitamin D3 derivatives on the innate immune system in HT-29 cells.
  • To elucidate the mechanism by which vitamin D3 derivatives exert anti-inflammatory effects.

Main Methods:

  • Flow cytometry to analyze Toll-like receptors (TLR) and CD14 expression.
  • Measurement of soluble CD14 (sCD14) release.
  • Analysis of extracellular signal-regulated kinase (ERK1/2) and p38 MAPK pathways.
  • Quantification of Interleukin-8 (IL-8) production stimulated by lipopolysaccharide (LPS).

Main Results:

  • Vitamin D3 derivatives up-regulated CD14 and increased sCD14 release in HT-29 cells.
  • 1α,25-dihydroxy-22-oxavitamin D3 (Oxa-D3) induced sCD14 release via ERK1/2 activation.
  • Vitamin D3 derivatives diminished LPS-stimulated IL-8 production.
  • Recombinant sCD14 neutralized LPS, reducing IL-8 production.

Conclusions:

  • Vitamin D3 derivatives, particularly Oxa-D3, promote sCD14 release through ERK1/2 signaling.
  • The anti-inflammatory effect is mediated by increased sCD14, which neutralizes LPS and reduces IL-8 production.
  • Vitamin D3 derivatives show potential for managing intestinal inflammation by modulating innate immune responses.