tetano
Editor, Senior Moderator
Acta Otolaryngol. 2019 Dec 18:1-8. doi: 10.1080/00016489.2019.1700304. [Epub ahead of print] [h=1]Influenza A virus infection induces indoleamine 2,3-dioxygenase (IDO) expression and modulates subsequent inflammatory mediators in nasal epithelial cells.[/h]
Lin YT[SUP]1,[/SUP][SUP]2[/SUP], Lin CF[SUP]1[/SUP], Yeh TH[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. 2 Graduate School of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 3 Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] IDO; Nasal epithelial cells; influenza virus; innate immunity; kynurenine; tryptophan
PMID: 31852346 DOI: 10.1080/00016489.2019.1700304
Lin YT[SUP]1,[/SUP][SUP]2[/SUP], Lin CF[SUP]1[/SUP], Yeh TH[SUP]1,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h] 1 Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. 2 Graduate School of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan. 3 Department of Otolaryngology, College of Medicine, National Taiwan University, Taipei, Taiwan.
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] IDO; Nasal epithelial cells; influenza virus; innate immunity; kynurenine; tryptophan
PMID: 31852346 DOI: 10.1080/00016489.2019.1700304