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
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiviral Agents / pharmacology*
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Ascorbic Acid / pharmacology*
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Biological Transport
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Bronchi / drug effects
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Bronchi / metabolism
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Cell Line, Transformed
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DEAD Box Protein 58 / genetics
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DEAD Box Protein 58 / metabolism
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Epithelial Cells / drug effects*
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Epithelial Cells / metabolism
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Gene Expression Regulation
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Humans
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Interferon Regulatory Factors / genetics
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Interferon Regulatory Factors / metabolism
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Interferon-Induced Helicase, IFIH1 / genetics*
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Interferon-Induced Helicase, IFIH1 / metabolism
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Interferon-alpha / antagonists & inhibitors
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Interferon-alpha / pharmacology
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Interleukin-8 / genetics
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Interleukin-8 / metabolism
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L-Gulonolactone Oxidase / deficiency
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L-Gulonolactone Oxidase / genetics
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Mice
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Mice, Knockout
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Myxovirus Resistance Proteins / genetics
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Myxovirus Resistance Proteins / metabolism
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Poly I-C / antagonists & inhibitors
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Poly I-C / pharmacology
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Receptors, Retinoic Acid / genetics*
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Receptors, Retinoic Acid / metabolism
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Sodium-Coupled Vitamin C Transporters / genetics*
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Sodium-Coupled Vitamin C Transporters / metabolism
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Transcriptome
Substances
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Antiviral Agents
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CXCL8 protein, human
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IL6 protein, human
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Interferon Regulatory Factors
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Interferon-alpha
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Interleukin-6
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Interleukin-8
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MX1 protein, human
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Myxovirus Resistance Proteins
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PLAAT4 protein, human
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Receptors, Immunologic
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Receptors, Retinoic Acid
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SLC23A2 protein, human
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Sodium-Coupled Vitamin C Transporters
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L-Gulonolactone Oxidase
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RIGI protein, human
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IFIH1 protein, human
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DEAD Box Protein 58
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Interferon-Induced Helicase, IFIH1
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Poly I-C
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Ascorbic Acid