1,25-Dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells.
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.
Equils
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Department of Pediatrics, Steven Speilberg Pediatric Research Center, Cedars-Sinai Medical Geffen School of Medicine at UCLA, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org
Naiki
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Shapiro
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Michelsen
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Adams
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Jordan
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D002460:Cell Line; D049109:Cell Proliferation; D018946:Chemokine CCL5 / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000032:analysis; D014162:Transfection / Q000379:methods; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
D018946:Chemokine CCL5; D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D; D007371:Interferon-gamma