Interleukin-1 receptor-associated kinase M (IRAK-M) promotes human rhinovirus infection in lung epithelial cells via the autophagic pathway

Wu, Qun; Dyk, Linda F. van; Jiang, Di; Dakhama, Azzeddine; Li, Liwu; White, Steven R.; Gross, Ashley; Chu, Hong Wei

doi:10.1016/j.virol.2013.08.005

Cited by 34 publications

(42 citation statements)

References 57 publications

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“…Polyinosine-polycytidylic acid (poly(I:C)) was purchased from Invivogen. Human rhinovirus serotype 1A (HRV-1A; ATCC) was propagated in H1-HeLa cells (CRL-1958; ATCC), purified, and titrated as described previously (41). Adenoviral expression constructs for TNFAIP3 (Ad-TNFAIP3) and GFP (Ad-GFP as control) have been previously described (36) and were prepared by Welgen.…”

Section: Methodsmentioning

confidence: 99%

Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects

Kadiyala

Sasse

Altonsy

et al. 2016

Journal of Biological Chemistry

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Antagonism of pro-inflammatory transcription factors by monomeric glucocorticoid receptor (GR) has long been viewed as central to glucocorticoid (GC) efficacy. However, the mechanisms and targets through which GCs exert therapeutic effects in diseases such as asthma remain incompletely understood. We previously defined a surprising cooperative interaction between GR and NF-B that enhanced expression of A20 (TNFAIP3), a potent inhibitor of NF-B. Here we extend this observation to establish that A20 is required for maximal cytokine repression by GCs. To ascertain the global extent of GR and NF-B cooperation, we determined genome-wide occupancy of GR, the p65 subunit of NF-B, and RNA polymerase II in airway epithelial cells treated with dexamethasone, TNF, or both using chromatin immunoprecipitation followed by deep sequencing. We found that GR recruits p65 to dimeric GR binding sites across the genome and discovered additional regulatory elements in which GR-p65 cooperation augments gene expression. GR targets regulated by this mechanism include key anti-inflammatory and injury response genes such as SERPINA1, which encodes ␣1 antitrypsin, and FOXP4, an inhibitor of mucus production. Although dexamethasone treatment reduced RNA polymerase II occupancy of TNF targets such as IL8 and TNFAIP2, we were unable to correlate specific binding sequences for GR or occupancy patterns with repressive effects on transcription. Our results suggest that cooperative anti-inflammatory gene regulation by GR and p65 contributes to GC efficacy, whereas tethering interactions between GR and p65 are not universally required for GC-based gene repression.

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Section: Methodsmentioning

confidence: 99%

Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects

Kadiyala

Sasse

Altonsy

et al. 2016

Journal of Biological Chemistry

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“…For example, human Tollip is required for the proper clearance of Huntington's disease-linked polyQ proteins through the ubiquitin-dependent autophagy [19]. As autophagy participates in the anti-RV response in a normal setting [10, 20], Tollip may also serve as a novel mechanism to modulate host responses to RV infection in a type 2 cytokine milieu (e.g., IL-13), a major feature of airway allergic inflammation.…”

Section: Introductionmentioning

confidence: 99%

Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection

Huang

Jiang

Francisco

et al. 2016

Clin Experimental Allergy

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Background Rhinovirus (RV) infection in asthma induces varying degrees of airway inflammation (e.g., neutrophils), but the underlying mechanisms remain unclear. Objective The major goal was to determine the role of genetic variation (e.g., single nucleotide polymorphisms [SNPs]) of Toll-interacting protein (Tollip) in airway epithelial responses to RV in a type 2 cytokine milieu. Methods DNA from blood of asthmatic and normal subjects was genotyped for Tollip SNP rs5743899 AA, AG and GG genotypes. Human tracheobronchial epithelial (HTBE) cells from donors without lung disease were cultured to determine pro-inflammatory and anti-viral responses to IL-13 and RV16. Tollip knockout and wild-type mice were challenged with house dust mite (HDM) and infected with RV1B to determine lung inflammation and anti-viral response. Results Asthmatic subjects carrying the AG or GG genotype (AG/GG) compared with the AA genotype demonstrated greater airflow limitation. HTBE cells with AG/GG expressed less Tollip. Upon IL-13 and RV16 treatment, cells with AG/GG (versus AA) produced more IL-8 and expressed less anti-viral genes, which was coupled with increased NF-κB activity and decreased expression of LC3, a hallmark of the autophagic pathway. Tollip co-localized and interacted with LC3. Inhibition of autophagy decreased anti-viral genes in IL-13 and RV16 treated cells. Upon HDM and RV1B, Tollip knockout (versus wild-type) mice demonstrated higher levels of lung neutrophilic inflammation and viral load, but lower levels of anti-viral gene expression. Conclusions and Clinical Relevance Our data suggest that Tollip SNP rs5743899 may predict varying airway response to RV infection in asthma.

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“…HRV-16 and HRV-1B (American Type Culture Collection, Manassas, VA) were propagated in H1-Hela cells (CRL-1958, ATCC) and purified as previously described [15]. Viral titer quantification was carried out by tissue culture infective dose per ml (TCID 50 /ml) in our cell culture experiments [16], and PFU/ml in our mouse model [15].…”

Section: Methodsmentioning

confidence: 99%

“…Viral titer quantification was carried out by tissue culture infective dose per ml (TCID 50 /ml) in our cell culture experiments [16], and PFU/ml in our mouse model [15]. …”

Section: Methodsmentioning

confidence: 99%

The Anti-inflammatory Effect of Alpha-1 Antitrypsin in Rhinovirus-infected Human Airway Epithelial Cells

Jiang

Berman

et al. 2016

J Clin Cell Immunol

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Objective Excessive airway inflammation is seen in chronic obstructive pulmonary disease (COPD) patients experiencing acute exacerbations, which are often associated with human rhinovirus (HRV) infection. Alpha-1 antitrypsin (A1AT) has anti-inflammatory function in endothelial cells and monocytes, but its anti-inflammatory effect has not been investigated in COPD airway epithelial cells. We determined A1AT’s anti-inflammatory function in COPD airway epithelial cells and the underlying mechanisms such as the role of caspase-1. Methods Brushed bronchial epithelial cells from COPD and normal subjects were cultured at air-liquid interface and treated with A1AT or bovine serum albumin (BSA, control) two hours prior to whole cigarette smoke (WCS) or air exposure, followed by HRV-16 infection. After 24 hours of viral infection, cell supernatants were collected for measuring IL-8, and cells were examined for caspase-1. The in vivo anti-inflammatory function of A1AT was determined by infecting mice intranasally with HRV-1B followed by aerosolized A1AT or BSA. Results A1AT significantly reduced WCS and HRV-16-induced IL-8 production in normal and COPD airway epithelial cells. COPD cells are less sensitive to A1AT’s anti-inflammatory effect than normal cells. A1AT exerted the anti-inflammatory function in part via reducing caspase-1 in normal cells, but not in COPD cells. In mice, A1AT significantly reduced HRV-1B induced lung neutrophilic inflammation. Conclusions A1AT exerts an anti-inflammatory effect in cigarette smoke-exposed and HRV-infected human airway epithelial cells, which may be related to its inhibitory effect on caspase-1 activity.

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Interleukin-1 receptor-associated kinase M (IRAK-M) promotes human rhinovirus infection in lung epithelial cells via the autophagic pathway

Cited by 34 publications

References 57 publications

Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects

Cistrome-based Cooperation between Airway Epithelial Glucocorticoid Receptor and NF-κB Orchestrates Anti-inflammatory Effects

Tollip SNP rs5743899 modulates human airway epithelial responses to rhinovirus infection

The Anti-inflammatory Effect of Alpha-1 Antitrypsin in Rhinovirus-infected Human Airway Epithelial Cells

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