1,25-Dihydroxyvitamin D3 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

Int J Mol Sci. 2022 Sep 13;23(18):10603. doi: 10.3390/ijms231810603.


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.

Keywords: 1,25(OH)2D3; JAK/STAT signaling pathway; NF-κB; PEDV; inflammation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antiviral Agents / pharmacology
  • Cell Line
  • Epithelial Cells / metabolism
  • Inflammation
  • Ligands
  • NF-KappaB Inhibitor alpha / metabolism
  • NF-kappa B / metabolism
  • Porcine epidemic diarrhea virus* / physiology
  • RNA, Small Interfering / pharmacology
  • Receptors, Calcitriol / metabolism
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction
  • Swine
  • Vitamin D / analogs & derivatives
  • Vitamin D / pharmacology


  • Anti-Inflammatory Agents
  • Antiviral Agents
  • Ligands
  • NF-kappa B
  • RNA, Small Interfering
  • Receptors, Calcitriol
  • STAT3 Transcription Factor
  • NF-KappaB Inhibitor alpha
  • Vitamin D
  • 1,25-dihydroxyvitamin D