Effects of 1,25-dihydroxyvitamin D3 in an ovalbumin-induced allergic rhinitis model
Effects of 1,25-dihydroxyvitamin D3 in an ovalbumin-induced allergic rhinitis model
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1,25-二羟基维生素 D3 在卵清蛋白诱导的过敏性鼻炎模型中的作用
DOI：
10.1016/j.intimp.2017.04.005
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发表时间：
2017-06-01
影响因子：
5.6
通讯作者：
Fan, Hua
中科院分区：
文献类型：
--
作者：
Chen, Baiwen;Qu, Shenhong;Fan, Hua
产生IL-17的Th 17细胞在变应性气道疾病中起重要作用，但其在变应性鼻炎（AR）中的局部表达和调控尚不清楚。本研究探讨了1，25-（OH）（2）D-3（1，25-dihydroxyvitamin D3，1，25-（OH）（2）D-3）对AR中T-bet表达、Th 1细胞、Th 2细胞、Th 17细胞和IL-33阳性上皮细胞的影响。C57 BL/6小鼠经鼻内用卵清蛋白（OVA）致敏，AR小鼠经腹腔注射1，25-（OH）（2）D-3。采用酶联免疫吸附试验检测细胞因子水平，流式细胞仪检测脾脏Th 1、Th 2和Th 17细胞表型，免疫荧光显微镜检测鼻咽相关淋巴组织（NALT）中CD 4（+）、IL-17（+）细胞和鼻粘膜中IL-33阳性细胞。AR小鼠脾脏中Th 2和Th 17细胞比例、血清中IL-17水平、NALF中IL-5和IL-13水平显著增加，但IL-33阳性上皮细胞数量和Th 1应答减少（脾脏中Th 1和Tbet（+）Th 1细胞比率和血清IFN-γ水平）比对照小鼠。1，25-（OH）（2）D-3处理显著减少打喷嚏次数，鼻摩擦、血清OVA-sIgE和IL-17、NALF中IL-5和IL-13水平、脾脏Th 17细胞比例和鼻粘膜组织学改变，但IL-33阳性上皮细胞数量增加。但1，25-（OH）（2）D-3处理对血清IFN-γ水平和脾脏Th 1、Tbet（+）Th 1和Th 2细胞比例无明显影响，提示1，25-（OH）（2）D-3可能通过抑制Th 17反应和局部IL-5和IL-13细胞因子的产生而发挥抗过敏作用。
IL-17-producing Th17 cells play an important role in allergic airway diseases, but their local expression and regulation in allergic rhinitis (AR) is not well understood. This study investigated the effects of 1,25dihydroxyvitamin D3 (1,25-(OH)(2)D-3)on T-bet expression, Th1 cells, Th2 cells, Th17 cells and IL-33-positive epithelial cells in AR. C57BL/6 mice were intranasally sensitized and challenged with ovalbumin (OVA), and 1,25-(OH)(2)D-3 was intraperitoneally injected into AR mice. Cytokine levels were measured with enzyme-linked immunosorbent assays, phenotypic analysis of Th1, Th2 and Th17 cells in the spleen was completed with flow cytometry, and the CD4(+) IL-17(+) cells in the Nasopharynx-associated lymphoid tissue (NALT) and IL-33-positive cells in nasal mucosa was evaluated with immunofluorescence microscopy. AR mice shown significantly increased Th2 and Th17 cell ratio in spleen, IL-17 level in serum, IL-5 and IL-13 levels in NALF but a lower number of IL-33-positive epithelial cells and Th1 response (Th1 and Tbet(+) Th1 cell ratio in the spleen and serum IFN-gamma level) than the control mice.1,25-(OH)(2)D-3 treatment significantly decreased the number of sneezing, nasal rubbing, OVA-sIgE and IL-17 in serum, IL-5 and IL-13 levels in NALF, Th17 cell ratio in the spleen and the histological of nasal mucosal but increased the number of IL-33-positive epithelial cells in AR mice. However, 1,25-(OH)(2)D-3 treatment did not significantly influence IFN-gamma level in serum, and Th1, Tbet(+) Th1 and Th2 cell ratio in spleen.Thus, 1,25-(OH)(2)D-3 may exert anti-allergic effects by suppressing Th17 responses and local production of IL-5 and IL-13 cytokines.