Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells

Biomolecules. 2021 Aug 3;11(8):1148. doi: 10.3390/biom11081148.

Abstract

Vitamin C is well documented to have antiviral functions; however, there is limited information about its effect on airway epithelial cells-the first cells to encounter infections. Here, we examined the effect of vitamin C on human bronchial epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells, and observed that sodium-dependent vitamin C transporter 2 (SVCT2) was the primary vitamin C transporter. Transcriptomic analysis revealed that treating BEAS-2B cells with vitamin C led to a significant upregulation of several metabolic pathways and interferon-stimulated genes (ISGs) along with a downregulation of pathways involved in lung injury and inflammation. Remarkably, vitamin C also enhanced the expression of the viral-sensing receptors retinoic acid-inducible gene 1 (RIG-1) and melanoma differentiation-associated protein 5 (MDA-5), which was confirmed at the protein and functional levels. In addition, the lungs of l-gulono-γ-lactone oxidase knockout (GULO-KO) mice also displayed a marked decrease in these genes compared to wild-type controls. Collectively, our findings indicate that vitamin C acts at multiple levels to exert its antiviral and protective functions in the lungs.

Keywords: GULO-KO mice; ISGs; airway epithelial cells; antiviral responses; vitamin C; vitamin C transporters.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Ascorbic Acid / pharmacology*
  • Biological Transport
  • Bronchi / drug effects
  • Bronchi / metabolism
  • Cell Line, Transformed
  • DEAD Box Protein 58 / genetics
  • DEAD Box Protein 58 / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression Regulation
  • Humans
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Interferon-Induced Helicase, IFIH1 / genetics*
  • Interferon-Induced Helicase, IFIH1 / metabolism
  • Interferon-alpha / antagonists & inhibitors
  • Interferon-alpha / pharmacology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • L-Gulonolactone Oxidase / deficiency
  • L-Gulonolactone Oxidase / genetics
  • Mice
  • Mice, Knockout
  • Myxovirus Resistance Proteins / genetics
  • Myxovirus Resistance Proteins / metabolism
  • Poly I-C / antagonists & inhibitors
  • Poly I-C / pharmacology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism
  • Receptors, Retinoic Acid / genetics*
  • Receptors, Retinoic Acid / metabolism
  • Sodium-Coupled Vitamin C Transporters / genetics*
  • Sodium-Coupled Vitamin C Transporters / metabolism
  • Transcriptome

Substances

  • Antiviral Agents
  • CXCL8 protein, human
  • IL6 protein, human
  • Interferon Regulatory Factors
  • Interferon-alpha
  • Interleukin-6
  • Interleukin-8
  • MX1 protein, human
  • Myxovirus Resistance Proteins
  • PLAAT4 protein, human
  • Receptors, Immunologic
  • Receptors, Retinoic Acid
  • SLC23A2 protein, human
  • Sodium-Coupled Vitamin C Transporters
  • L-Gulonolactone Oxidase
  • DDX58 protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C
  • Ascorbic Acid