Effects of vitamin D on airway epithelial cell morphology and rhinovirus replication.

Effects of vitamin D on airway epithelial cell morphology and rhinovirus replication.
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DOI:
10.1371/journal.pone.0086755
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Gern JE
Gern JE
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Brockman-Schneider RA;Pickles RJ;Gern JE

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维生素D与降低病毒性呼吸道疾病的风险有关。我们假设维生素D可以直接减少鼻病毒(RV)在气道上皮细胞中的复制。用维生素D处理原代人支气管上皮细胞(hBEC),通过定量PCR评价RV复制和基因表达。通过ELISA测量细胞因子/趋化因子分泌,并使用伏安计测定跨上皮电阻(TER)。采用免疫组织化学方法进行形态学检查。补充维生素D对RV复制没有显著影响,但增强了感染或未感染细胞的CXCL 8和CXCL 10分泌。用1,25(OH)2D形式的维生素D处理引起细胞形态的显著变化,包括细胞层增厚(中位数为46.5 µm [35.0-69.0] vs. 30 µm [24.5-34.2],p<0.01)和细胞角蛋白-5表达细胞的增殖,如免疫组织化学分析所示。25(OH)D也有类似的作用。除了改变形态外,较高浓度的维生素D还显著上调了富含脯氨酸的小蛋白(SPRR 1 β)的表达(6.3倍诱导,p<0.01),提示鳞状化生。维生素D处理hBEC不会改变机械诱导伤口的修复。总的来说,这些研究结果表明,维生素D不直接影响呼吸道上皮细胞中的RV复制,但可以影响趋化因子的合成,改变呼吸道上皮细胞的生长和分化。
Vitamin D has been linked to reduced risk of viral respiratory illness. We hypothesized that vitamin D could directly reduce rhinovirus (RV) replication in airway epithelium. Primary human bronchial epithelial cells (hBEC) were treated with vitamin D, and RV replication and gene expression were evaluated by quantitative PCR. Cytokine/chemokine secretion was measured by ELISA, and transepithelial resistance (TER) was determined using a voltohmmeter. Morphology was examined using immunohistochemistry. Vitamin D supplementation had no significant effects on RV replication, but potentiated secretion of CXCL8 and CXCL10 from infected or uninfected cells. Treatment with vitamin D in the form of 1,25(OH)2D caused significant changes in cell morphology, including thickening of the cell layers (median of 46.5 µm [35.0–69.0] vs. 30 µm [24.5–34.2], p<0.01) and proliferation of cytokeratin-5-expressing cells, as demonstrated by immunohistochemical analysis. Similar effects were seen for 25(OH)D. In addition to altering morphology, higher concentrations of vitamin D significantly upregulated small proline-rich protein (SPRR1β) expression (6.3 fold-induction, p<0.01), suggestive of squamous metaplasia. Vitamin D treatment of hBECs did not alter repair of mechanically induced wounds. Collectively, these findings indicate that vitamin D does not directly affect RV replication in airway epithelial cells, but can influence chemokine synthesis and alters the growth and differentiation of airway epithelial cells.
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