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Vitamin D treatment reduces inflammatory cytokine secretion by pollution-stimulated bronchial epithelial cells

Pfeffer, PE, Dr ; Kelly, FJ ; Hawrylowicz, CM

The Lancet (British edition), 2013-02, Vol.381, p.S87-S87 [Periódico revisado por pares]

London: Elsevier Ltd

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  • Título:
    Vitamin D treatment reduces inflammatory cytokine secretion by pollution-stimulated bronchial epithelial cells
  • Autor: Pfeffer, PE, Dr ; Kelly, FJ ; Hawrylowicz, CM
  • Assuntos: air pollution ; asthma ; cell viability ; chemokines ; environmental factors ; epithelial cells ; gene expression ; gene expression regulation ; genes ; granulocyte-macrophage colony-stimulating factor ; humans ; inflammation ; interleukin-6 ; Internal Medicine ; microarray technology ; particulates ; quantitative polymerase chain reaction ; secretion ; T-lymphocytes ; vitamin D
  • É parte de: The Lancet (British edition), 2013-02, Vol.381, p.S87-S87
  • Notas: http://dx.doi.org/10.1016/S0140-6736(13)60527-9
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  • Descrição: Abstract Background Environmental factors have a strong causal role in the development of asthma. Vitamin D insufficiency and particulate matter (PM) air pollution are two environmental factors associated with airways disease. We hypothesise that vitamin D will reduce production of inflammatory mediators by bronchial epithelial cells stimulated with PM, protecting the airways from inflammation that would otherwise promote Th2/Th17 responses in asthma. Methods Primary human bronchial epithelial cells from healthy and asthmatic donors were cultured with standardised PM with or without vitamin D. Activated 1,25(OH)D3 was used in preliminary experiments and the precursor 25(OH)D3 in later experiments. A transcription microarray was conducted to highlight differentially expressed inflammatory mediators for further investigation. Expression of target genes was measured by quantitative real-time PCR and levels of inflammatory cytokines in culture supernatants by Cytometric Bead Array. Findings PM caused increased production of multiple cytokines and chemokines by bronchial epithelial cells. Vitamin D decreased production of a range of cytokines and chemokines, including interleukin (IL) 6 (47·8% [95% CI 5·3%–90·3%] reduction in gene expression with 1,25(OH)D3, 46·7% [35·6%–57·8%] decrease in supernatant protein) and IL24 (61.3% [95% CI 36·0%–86.5%] reduction in gene expression). This reduction was not due to loss of cell viability. Other cytokines were not affected by vitamin D—for example, granulocyte-macrophage colony-stimulating factor (12·9% [95% CI −19·5% to 45·4%] reduction in gene expression, 1·9% [–16·7% to 20·5%] in supernatant protein). Interpretation The decrease in IL-6 production on treating PM-stimulated bronchial cells with vitamin D, either active 1,25(OH)D3 or the circulating precursor 25(OH)D3, is important given that IL6 inhibits regulatory T-cell responses and promotes Th17 responses. IL24 promotes Th1 cytokine secretion. Functional studies investigating the effect of epithelial-conditioned medium on T cells are in progress. Funding Wellcome Trust and National Institute for Health Research.
  • Editor: London: Elsevier Ltd
  • Idioma: Inglês

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