1,25-Dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells

Clin Exp Immunol. 2006 Jan;143(1):58-64. doi: 10.1111/j.1365-2249.2005.02961.x.

Abstract

In addition to its well-known role in mineral and skeletal homeostasis, 1,25-dihydroxyvitamin D3 [1,25-(OH)2, D3] regulates the differentiation, growth and function of a broad range of immune system cells, including monocytes, dendritic cells, T and B lymphocytes. Vascular endothelial cells play a major role in the innate immune activation during infections, sepsis and transplant rejection; however, currently there are no data on the effect of 1,25-(OH)2 D3 on microbial antigen-induced endothelial cell activation. Here we show that 1,25-(OH)2 D3 pretreatment of human microvessel endothelial cells (HMEC) inhibited the enteric gram-negative bacterial lipopolysaccharide (LPS) activation of transcription factor NF-kappaB and interleukin (IL)-6, IL-8 and regulated upon activation normal T cell exposed and secreted (RANTES) release. The effect of 1,25-(OH)2 D3 was not due to increased cell death or inhibition of endothelial cell proliferation. 1,25-(OH)2 D3 pretreatment of HMEC did not block MyD88-independent LPS-induced interferon (IFN)-beta promoter activation. 1,25-(OH)2 D3 pretreatment of HMEC did not modulate Toll-like receptor 4 (TLR4) or MD-2 expression. These data suggest that 1,25-(OH)2 D3 may play a role in LPS-induced immune activation of endothelial cells during gram-negative bacterial infections, and a suggest a potential role for 1,25-(OH)2 D3 and its analogues as an adjuvant in the treatment of gram-negative sepsis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Chemokine CCL5 / analysis
  • Cytokines / analysis*
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology*
  • Gene Expression / drug effects
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Interferon-gamma / genetics
  • Interleukin-6 / analysis
  • Interleukin-8 / analysis
  • Lipopolysaccharides / pharmacology*
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Toll-Like Receptor 4 / analysis
  • Transfection / methods
  • Vitamin D / analogs & derivatives*
  • Vitamin D / pharmacology

Substances

  • Chemokine CCL5
  • Cytokines
  • Immunosuppressive Agents
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Vitamin D
  • 1,25-dihydroxyvitamin D
  • Interferon-gamma