Cited by 513Immune Response and InflammationVitamin D Research StudiesImmune responses and vaccinations

Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns

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Sadeghi, Kambis, Wessner, Barbara, Laggner, Ute, Ploder, Martin, Tamandl, Dietmar, Friedl, Josef, Zügel, Ullrich, Steinmeyer, Andreas +4 more·2006·European Journal of Immunology

Abstract

Toll-like receptors (TLR) represent an ancient front-line defence system that enables the host organism to sense the presence of microbial components within minutes. As inducers of inflammation, TLR act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation. We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion. Despite 1,25(OH)(2)D3-induced up-regulation of CD14, challenge of human monocytes with either LPS or lipoteichoic acid resulted in impaired TNF-alpha and procoagulatory tissue factor (CD142) production, emphasizing the critical role of TLR in the induction of inflammation. Moreover, reduced TLR levels in 1,25(OH)(2)D3-treated phagocytes were accompanied by impaired NF-kappaB/RelA translocation to the nucleus and by reduced p38 and p42/44 (extracellular signal-regulated kinase 1/2) phosphorylation upon TLR-ligand engagement. Both TLR down-regulation and CD14 up-regulation were substantially inhibited by the vitamin D receptor (VDR) antagonist ZK 159222, indicating that the immunomodulatory effect of 1,25(OH)(2)D3 on innate immunity receptors requires VDR transcription factor activation. Our data provide strong evidence that 1,25(OH)(2)D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR-dependent mechanism, most likely due to decreased levels of TLR2 and TLR4.

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Crossref · 10.1002/eji.200425995

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  • FoxO proteins regulate genes involved in energy homeostasis, cell survival, and inflammatory responses including NF-kB.

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Authors
Sadeghi, K., Wessner, B., Laggner, U., Ploder, M., Tamandl, D., Friedl, J., Zügel, U., Steinmeyer, A., Pollak, A., Roth, E., Boltz‐Nitulescu, G., & Spittler, A.
Affiliations
Medical University of Vienna (AT)
Corresponding author
Spittler, Andreas
Venue
European Journal of Immunology
Publisher
Wiley
Published
2006-02
Volume
36
Issue
2
Pages
361-370
ISSN
  • 0014-2980 (ISSN-L)
  • 1521-4141
OpenAlex
W1985558958
Cited by
513
References
35
Citations by year
2026: 14 · 2025: 16 · 2024: 13 · 2023: 27 · 2022: 29 · 2021: 41 · 2020: 27 · 2019: 23 · 2018: 28 · 2017: 26 · 2016: 27 · 2015: 40 · 2014: 31 · 2013: 30 · 2012: 49
FWCI
6.03
Type
journal article
Language
en
Open access
Locations
  • European Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
vitamin D3, 1,25-dihydroxyvitamin D3, vitamin D receptor, TLR2, TLR4, monocytes, innate immunity, CD14, lipopolysaccharide, lipoteichoic acid, TNF-α, tissue factor, MAPK signaling, immunomodulation, bacterial cell wall components
MeSH terms
Calcitriol, Cells, Cultured, Cholecalciferol, Dose-Response Relationship, Drug, Humans, Inflammation, Lipopolysaccharides, Macrophage Activation, Monocytes, Phosphorylation, Teichoic Acids, Signal Transduction, Down-Regulation, Up-Regulation, Receptors, Calcitriol, Lipopolysaccharide Receptors, Mitogen-Activated Protein Kinase 1, Active Transport, Cell Nucleus, p38 Mitogen-Activated Protein Kinases, Toll-Like Receptor 2, Toll-Like Receptor 4, Transcription Factor RelA

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