Dengue/Chikungunya Group, ICMR-National Institute of Virology, 20A, Dr Ambedkar Road, Pune 411001, Maharashtra, India.
Dengue/Chikungunya Group, ICMR-National Institute of Virology, 20A, Dr Ambedkar Road, Pune 411001, Maharashtra, India.
Int Immunopharmacol. 2018 Sep;62:237-243. doi: 10.1016/j.intimp.2018.07.019. Epub 2018 Jul 20.
Dengue virus (DENV) infections are straining public health systems worldwide. Vitamin D, a secosteroid hormone, is currently being investigated for its immunomodulatory effects in DENV infections. The objectives of the present study was to study the effect of 1, 25 dihydroxy vitamin D3 (1,25(OH)D) on the expression of genes coding for RNA sensing pattern recognition receptors, downstream signaling components including oligoadenylate synthetases (OAS) and interferon stimulated gene 15 (ISG15) and T helper (Th)1, Th2 and Th17 cytokine response in DENV infected U937-DC-SIGN cells and THP-1 macrophages. U937-DC-SIGN RNA was investigated for the expression of TLR3, DDX58, IFIH1, OAS1, OAS2, OAS3, CAMP and ISG15 genes using gene expression assays. Interleukin (IL)-12p70, IL-10, IL-4 and IL-17A levels were assessed in the THP-1 macrophage culture supernatants. The results revealed that 1,25(OH)D increased the expression of DDX58, OAS1, OAS2 and OAS3 at 0.1 μM while higher concentration had diminishing effect. 1,25(OH)D enhanced the expression of ISG15 and CAMP genes. 1,25(OH)D suppressed the levels of IL-4 and IL-17A. Lower concentration of 1,25(OH)D suppressed IL-12p70 and IL-10 levels while a higher concentration enhanced the levels. The results suggest that 1,25(OH)D may have concentration dependent immunomodulatory effects. Higher dose of 1,25(OH)D might have an immunoregulatory role in ameliorating inflammation during dengue infections. Further studies are needed to evaluate the efficacy of different doses of 1,25(OH)D in preventing severe dengue.
登革热病毒（DENV）感染正在给全球公共卫生系统带来压力。维生素 D 是一种固醇类激素，目前正在研究其在 DENV 感染中的免疫调节作用。本研究的目的是研究 1,25 二羟维生素 D3（1,25（OH）D）对 DENV 感染的 U937-DC-SIGN 细胞和 THP-1 巨噬细胞中编码 RNA 感应模式识别受体、下游信号成分（包括寡聚腺苷酸合成酶（OAS）和干扰素刺激基因 15（ISG15））以及 T 辅助（Th）1、Th2 和 Th17 细胞因子反应的基因表达的影响。使用基因表达测定法研究了 U937-DC-SIGN RNA 中 TLR3、DDX58、IFIH1、OAS1、OAS2、OAS3、CAMP 和 ISG15 基因的表达。评估了 THP-1 巨噬细胞培养上清液中白细胞介素（IL）-12p70、IL-10、IL-4 和 IL-17A 的水平。结果表明，1,25（OH）D 在 0.1 μM 时增加了 DDX58、OAS1、OAS2 和 OAS3 的表达，而更高浓度则有减弱作用。1,25（OH）D 增强了 ISG15 和 CAMP 基因的表达。1,25（OH）D 抑制了 IL-4 和 IL-17A 的水平。1,25（OH）D 的低浓度抑制了 IL-12p70 和 IL-10 的水平，而高浓度则增强了它们的水平。结果表明，1,25（OH）D 可能具有浓度依赖性的免疫调节作用。更高剂量的 1,25（OH）D 在改善登革热感染期间的炎症方面可能具有免疫调节作用。需要进一步研究来评估不同剂量的 1,25（OH）D 在预防严重登革热方面的疗效。
