1,25-Dihydroxyvitamin D(3) Negatively Regulates the Inflammatory Response to Porcine Epidemic Diarrhea Virus Infection by Inhibiting NF-κB and JAK/STAT Signaling Pathway in IPEC-J2 Porcine Epithelial Cells.
1,25-Dihydroxyvitamin D(3) Negatively Regulates the Inflammatory Response to Porcine Epidemic Diarrhea Virus Infection by Inhibiting NF-κB and JAK/STAT Signaling Pathway in IPEC-J2 Porcine Epithelial Cells.
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1，25-二羟基维生素D（3）通过抑制IPEC-J2猪上皮细胞NF-κB和JAK/STAT信号通路负性调节猪流行性腹泻病毒感染的炎症反应
DOI：
10.3390/ijms231810603
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发表时间：
2022-09-13
影响因子：
5.6
通讯作者：
Yu, Bing
中科院分区：
文献类型：
--
作者：
Yang, Jiwen;Chen, Daiwen;Tian, Gang;Mao, Xiangbing;He, Jun;Zheng, Ping;Yu, Jie;Luo, Yuheng;Luo, Junqiu;Huang, Zhiqing;Wu, Aimin;Yan, Hui;Yu, Bing
猪流行性腹泻病毒（PEDV）感染会导致小猪出现水样腹泻和呕吐。PEDV感染的发病机制与肠道炎症有关。已知1，25-二羟维生素D3（1，25（OH）2D 3）具有有效的抗炎活性，但1，25（OH）2D 3是否能抑制PEDV诱导的炎症反应及其机制尚不清楚。我们采用转录组分析、基因和蛋白表达、RNA干扰和过表达等技术研究了1，25（OH）2D 3对PEDV感染IPEC-J2细胞的抗炎作用。结果显示，随着PEDV感染时间的延长，IPEC-J2细胞中IL-19和C-C基序趋化因子配体20（CCL 20）基因表达增强。有趣的是，1，25（OH）2D 3补充明显抑制PEDV诱导的IL-19和CCL 20表达。同时，我们还发现1，25（OH）2D 3在感染后24 h降低了PEDV诱导的p-NF-κB、p-STAT 1和p-STAT 3蛋白水平。在PEDV感染后，IκBα和SOCS 3、NF-κB和STAT抑制剂分别被1，25（OH）2D 3补充增加。另外，1，25（OH）2D 3补充抑制由PEDV诱导的ISG 15和MxA表达。1，25（OH）2D 3虽然抑制JAK/STAT信号通路和抗病毒基因表达，但对PEDV的复制和IFN-α诱导的抗病毒作用无明显影响。此外，当维生素D受体（VDR）被siRNA沉默时，1，25（OH）2D 3的抗炎作用被抑制。同时，VDR过表达可显著下调PEDV感染诱导的IL-19和CCL 20表达。总之，我们的结果提供了强有力的证据，即1，25（OH）2D 3可以通过VDR调节NF-κB和JAK/STAT信号通路来减轻PEDV诱导的炎症。这些结果表明，维生素D可以有助于抑制肠道炎症和减轻肠道损伤的PEDV感染的仔猪，这为开发营养策略，以防止PEDV感染仔猪提供了新的途径。
Porcine epidemic diarrhea virus (PEDV) infection causes watery diarrhea and vomiting in piglets. The pathogenesis of PEDV infection is related to intestinal inflammation. It is known that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has potent anti-inflammatory activity, but it is unknown whether 1,25(OH)2D3 can inhibit the PEDV-induced inflammatory response and the underlying mechanism. We used transcriptome analysis, gene and protein expression, RNA interference and overexpression, and other techniques to study the anti-inflammatory effects of 1,25(OH)2D3 on PEDV infection in IPEC-J2 cells. The results showed that interleukin 19 (IL-19) and C-C motif chemokine ligand 20 (CCL20) gene expression were enhanced with the increase in PEDV infection time in IPEC-J2 cells. Interestingly, 1,25(OH)2D3 supplementation obviously inhibited IL-19 and CCL20 expression induced by PEDV. Meanwhile, we also found that 1,25(OH)2D3 reduced p-NF-κB, p-STAT1, and p-STAT3 protein levels induced by PEDV at 24 h post-infection. IκBα and SOCS3, NF-κB, and STAT inhibitor respectively, were increased by 1,25(OH)2D3 supplementation upon PEDV infection. In addition, 1,25(OH)2D3 supplementation inhibited ISG15 and MxA expression induced by PEDV. Although 1,25(OH)2D3 suppressed the JAK/STAT signal pathway and antiviral gene expression, it had no significant effects on PEDV replication and IFN-α-induced antiviral effects. In addition, when the vitamin D receptor (VDR) was silenced by siRNA, the anti-inflammatory effect of 1,25(OH)2D3 was inhibited. Meanwhile, the overexpression of VDR significantly downregulated IL-19 and CCL20 expression induced by PEDV infection. Together, our results provide powerful evidence that 1,25(OH)2D3 could alleviate PEDV-induced inflammation by regulating the NF-κB and JAK/STAT signaling pathways through VDR. These results suggest that vitamin D could contribute to inhibiting intestinal inflammation and alleviating intestinal damage in PEDV-infected piglets, which offers new approaches for the development of nutritional strategies to prevent PEDV infection in piglets.
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DOI：
10.1186/s12950-018-0195-6
发表时间：
2018
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Huang KY;Hsu YH;Chen WY;Tsai HL;Yan JJ;Wang JD;Liu WL;Lin RM
通讯作者：
Lin RM
影响因子：
2.4
作者：
Madson, D. M.;Arruda, P. H. E.;Yoon, K. J.
通讯作者：
Yoon, K. J.
影响因子：
7.3
作者：
Anderson, Jeremy;Do, Lien Anh Ha;Licciardi, Paul V.
通讯作者：
Licciardi, Paul V.
DOI：
10.1016/j.bbrc.2005.01.110
发表时间：
2005-04-01
影响因子：
3.1
作者：
Choi, WH;Ji, KA;Joe, EH
通讯作者：
Joe, EH
影响因子：
2.4
作者：
Jung K;Miyazaki A;Saif LJ
通讯作者：
Saif LJ