1. Influenza A virus infection induces indoleamine 2,3-dioxygenase (IDO) expression and modulates subsequent inflammatory mediators in nasal epithelial cells.
- Author
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Lin, Yi-Tsen, Lin, Chih-Feng, and Yeh, Te-Huei
- Subjects
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CELL culture , *CYTOKINES , *EPITHELIAL cells , *GRANULOCYTE-colony stimulating factor , *GENE expression , *INFLUENZA , *INTERLEUKINS , *NASAL mucosa , *POLYMERASE chain reaction , *TRYPTOPHAN , *INFLUENZA A virus , *REVERSE transcriptase polymerase chain reaction , *METABOLOMICS - Abstract
Background: Nasal epithelial cells are the first site of encounter of the influenza virus, and their innate immune response might define subsequent inflammatory direction. Aims/objectives: We used metabolomics analysis to identify metabolic changes and the regulation of inflammatory cytokines in nasal epithelial cells upon influenza virus infection. Material and methods: We cultured nasal epithelial cells using air-liquid interface (ALI) model. Influenza virus (PR8) infection followed by metabolomic analysis was performed. Furthermore, cytokine expression was analyzed by cytokine array and RT-qPCR. Results: Metabolomic analysis revealed depletion of the tryptophan and accumulation of its metabolite, kynurenine, within 48 h. The major enzyme involved in the tryptophan metabolic pathway, indoleamine 2,3-dioxygenase (IDO), was overexpressed after infection. Cytokine expression array after infection showed increased levels of IL-1α, CCL2, IL-6, CXCL10, CCL5, and CXCL11, and after using 1-methyltryptophan (1-MT) as inhibitor, the expression levels of IL-6 and G-CSF were reduced. Conclusions and significance: Viral infection results in depletion of tryptophan and accumulation of kynurenine via increased cellular IDO activity. Inhibition of IDO activity or replenishment of tryptophan by local application may be a good therapeutic strategy for limiting the initial damage caused by influenza virus in nasal epithelial cells. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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