Limits...
Trehalose-mediated autophagy impairs the anti-viral function of human primary airway epithelial cells.

Wu Q, Jiang D, Huang C, van Dyk LF, Li L, Chu HW - PLoS ONE (2015)

Bottom Line: We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load.Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5) effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load.Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.

ABSTRACT
Human rhinovirus (HRV) is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5) effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I) and IFN-β promoter stimulator 1 (IPS-1), two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

No MeSH data available.


Related in: MedlinePlus

Trehalose induces autophagy in normal human primary airway epithelial cells.Normal human tracheobronchial epithelial cells were treated with medium or trehalose (TRE, 100 mM) for 48 h and then infected with HRV-16 (104 TCID50/well) for 2 h. After removing the free viruses, cells were incubated with medium or trehalose for additional 6 h. Protein levels of LC3 I and LC3 II were examined by Western blot analysis with GAPDH protein used as loading control. Data are expressed as mean ± SEM (A) (n = 5 independent experiments, * p<0.05). A representative Western blot picture of LC3 I and LC3 II (B) was shown from 5 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4400043&req=5

pone.0124524.g002: Trehalose induces autophagy in normal human primary airway epithelial cells.Normal human tracheobronchial epithelial cells were treated with medium or trehalose (TRE, 100 mM) for 48 h and then infected with HRV-16 (104 TCID50/well) for 2 h. After removing the free viruses, cells were incubated with medium or trehalose for additional 6 h. Protein levels of LC3 I and LC3 II were examined by Western blot analysis with GAPDH protein used as loading control. Data are expressed as mean ± SEM (A) (n = 5 independent experiments, * p<0.05). A representative Western blot picture of LC3 I and LC3 II (B) was shown from 5 independent experiments.

Mentions: As the 6 h post HRV-16 infection presented the most significant changes of IFN-λ1 expression and viral load with trehalose treatment, we focused on this early time-point to examine the induction of autophagy by trehalose in normal human primary airway epithelial cells. We measured LC3 I and LC3 II protein levels in NHTE cells after treatment with or without trehalose and HRV-16 for 6 h. Without HRV-16 infection, trehalose treatment notably increased accumulation of LC3 II protein compared with medium control (Fig 2). In line with our previous finding that HRV-16 induces autophagy in a human NCI-H292 lung epithelial cell line [32], HRV-16 infection significantly increased the ratio of LC3 II/LC3 I protein in NHTE cells. Trehalose treatment robustly increased LC3 II protein levels following HRV-16 infection as compared to medium-treated and HRV-infected cells.


Trehalose-mediated autophagy impairs the anti-viral function of human primary airway epithelial cells.

Wu Q, Jiang D, Huang C, van Dyk LF, Li L, Chu HW - PLoS ONE (2015)

Trehalose induces autophagy in normal human primary airway epithelial cells.Normal human tracheobronchial epithelial cells were treated with medium or trehalose (TRE, 100 mM) for 48 h and then infected with HRV-16 (104 TCID50/well) for 2 h. After removing the free viruses, cells were incubated with medium or trehalose for additional 6 h. Protein levels of LC3 I and LC3 II were examined by Western blot analysis with GAPDH protein used as loading control. Data are expressed as mean ± SEM (A) (n = 5 independent experiments, * p<0.05). A representative Western blot picture of LC3 I and LC3 II (B) was shown from 5 independent experiments.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4400043&req=5

pone.0124524.g002: Trehalose induces autophagy in normal human primary airway epithelial cells.Normal human tracheobronchial epithelial cells were treated with medium or trehalose (TRE, 100 mM) for 48 h and then infected with HRV-16 (104 TCID50/well) for 2 h. After removing the free viruses, cells were incubated with medium or trehalose for additional 6 h. Protein levels of LC3 I and LC3 II were examined by Western blot analysis with GAPDH protein used as loading control. Data are expressed as mean ± SEM (A) (n = 5 independent experiments, * p<0.05). A representative Western blot picture of LC3 I and LC3 II (B) was shown from 5 independent experiments.
Mentions: As the 6 h post HRV-16 infection presented the most significant changes of IFN-λ1 expression and viral load with trehalose treatment, we focused on this early time-point to examine the induction of autophagy by trehalose in normal human primary airway epithelial cells. We measured LC3 I and LC3 II protein levels in NHTE cells after treatment with or without trehalose and HRV-16 for 6 h. Without HRV-16 infection, trehalose treatment notably increased accumulation of LC3 II protein compared with medium control (Fig 2). In line with our previous finding that HRV-16 induces autophagy in a human NCI-H292 lung epithelial cell line [32], HRV-16 infection significantly increased the ratio of LC3 II/LC3 I protein in NHTE cells. Trehalose treatment robustly increased LC3 II protein levels following HRV-16 infection as compared to medium-treated and HRV-infected cells.

Bottom Line: We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load.Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5) effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load.Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, National Jewish Health, Denver, Colorado, United States of America.

ABSTRACT
Human rhinovirus (HRV) is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5) effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I) and IFN-β promoter stimulator 1 (IPS-1), two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations.

No MeSH data available.


Related in: MedlinePlus