Human rhinoviruses (HRV) are common cold viruses associated with exacerbations of lower airways diseases. Although viral induced epithelial damage mediates inflammation, the molecular mechanisms responsible for airway and dysfunction remain undefined. Using experimental HRV infection studies in highly differentiated human bronchial cells grown at air-liquid interface (ALI), we examine links between host defense, cellular metabolism, barrier function. We observe that early HRV-C15 induces a...

Human rhinovirus (HRV) infections are the primary cause of common cold and a major trigger for exacerbations lower airway diseases, such as asthma chronic obstructive pulmonary diseases. Although human bronchial epithelial cells (HBE) natural host HRV infections, much our understanding how replicates induces antiviral responses is based on studies using non-airway cell lines (e.g. HeLa cells). The current study examines replication cycle HRV, responses, in highly differentiated cultures HBE....

Abstract Virus–bacteria coinfections are associated with more severe exacerbations and increased risk of hospital readmission in patients chronic obstructive pulmonary disease (COPD). The airway epithelium responds to such infections by releasing proinflammatory antimicrobial cytokines, including IL-17C. However, the regulation role IL-17C is not well understood. In this study, we examine mechanisms regulating production its potential COPD exacerbations. Human bronchial epithelial cells...

Submerged cultures of primary human airway epithelial cells or cell lines have been a mainstay biology research for decades due to their robust in vitro proliferative capacity, relatively low maintenance culture conditions, and clinically translatable results nasal bronchial brushings. With the development improvement air-liquid interface (ALI) cells, such considered superior immortalized monolayers, as effectively recapitulate vivo architecture types. Although ALI growth protocols are...

Triple-negative breast cancer (TNBC) is a highly aggressive and metastatic form of that lacks an effective targeted therapy. To identify new therapeutic targets, we investigated the phosphohistidine phosphatase, LHPP, which has been implicated in development several types cancer. However, full significance LHPP progression remains unclear due to our limited understanding its molecular mechanism. We found levels phosphatase were significantly increased human patients compared normal adjacent...

While glucocorticoids act via the glucocorticoid receptor (GR; NR3C1) to reduce expression of many inflammatory genes, repression is not an invariable outcome. Here, we explore synergy occurring between synthetic (dexamethasone and budesonide) proinflammatory cytokines (IL1B TNF) on toll-like 2 (TLR2). This effect observed in epithelial cell lines both undifferentiated differentiated primary human bronchial cells (pHBECs). In A549 cells, IL1B-plus-glucocorticoid-induced TLR2 required nuclear...

Human rhinovirus (HRV) is a major trigger of acute exacerbations both asthma and chronic obstructive pulmonary disease. The airway epithelium the primary site HRV infection, responds by releasing proinflammatory antimicrobial cytokines. Epithelial cells release IL-17C in response to exposure bacterial, viral fungal pathogens. We previously demonstrated role for production from undifferentiated epithelial cells, showed that could play neutrophil recruitment. To extend these observations,...

Ligand-activated glucocorticoid receptor (GR) elicits variable glucocorticoid-modulated transcriptomes in different cell types. However, some genes, including Krüppel-like factor 9 (KLF9), a putative transcriptional repressor, demonstrate conserved responses. We show that glucocorticoids induce KLF9 expression the human airways vivo and differentiated bronchial epithelial (HBE) cells grown at air–liquid interface (ALI). In A549 BEAS-2B pulmonary cells, with similar kinetics to primary HBE...

There is a clear, unmet clinical need to identify new drugs treat individuals with asthma, chronic obstructive pulmonary disease (COPD), and idiopathic fibrosis (IPF) in whom current medications are either inactive or suboptimal. In preclinical models, EP₄-receptor agonists display efficacy, but their mechanism of action unclear. this study, using human bronchial epithelial cells as therapeutically relevant drug target, we hypothesized that changes gene expression may play an...

Chronic use of <i>β</i>₂-adrenoceptor agonists as a monotherapy in asthma is associated with loss disease control and an increased risk mortality. Herein, we tested the hypothesis that agonists, including formoterol, <i>promote</i> biased, <i>β</i>-arrestin (Arr) 2–dependent activation mitogen-activated protein kinases, ERK1/2, human airway epithelial cells and, thereby, effect changes gene expression could contribute to their adverse clinical outcomes. Three cell models were...

Inflammatory bowel diseases (IBD) are chronic inflammatory in which abdominal pain, bloody diarrhea, weight loss, and fatigue collectively result diminished quality of patient life. The disappearance intestinal helminth infections Western societies is associated with an increased prevalence IBD other immune-mediated diseases. Evidence indicates that helminths induce tolerogenic dendritic cells (tolDCs), promote tolerance attenuate inflammation characteristic IBD, but the exact mechanism...

RATIONALE Human rhinoviruses (HRV) are responsible for over 50% of viral respiratory tract infections, and pose a significant health challenge sufferers chronic inflammatory airway diseases. Much our current knowledge the HRV lifecycle is based on other picornavirus models using cell lines non‐airway origin (e.g. HeLa cells). However, human epithelial (HAE) natural host that subject to infection replication. Using highly‐differentiated HAE, we seek elucidate mechanisms uses remodel cellular...

RATIONALE Infections with human rhinovirus (HRV)‐C strains are associated more severe exacerbations and increased hospitalizations in children asthma. Although the replication cycles of HRV‐A B have been extensively studied using cells non‐airway origin (e.g. HeLa cells), HRV‐C within airway epithelial (HAE) remains poorly understood as exclusively infects highly‐differentiated HAE. We recently shown that HRV infections can be completely cleared from HAE without any requirement for immune...

Long‐acting β 2 ‐adrenoceptor agonists (LABAs) are mainstay drugs used routinely in asthma management. Our recent work revealed that (β2‐AR) promote a significant number of gene expression changes BEAS‐2B airway epithelial cells could contribute to their therapeutic activity and adverse effects (AEs) asthma. In this study, we investigated the extent which canonical (G‐protein/cAMP/protein kinase A [PKA]) non‐canonical (β‐arrestin/extracellular signal‐regulated [ERK]) signalling regulate...

RATIONALE Glucocorticoids (GCs) are stress hormones that act on the GC receptor (GR; NR3C1) to elicit effects, including repression of inflammatory gene expression. The mechanisms by which GR modulate expression not completely understood. binds thousands genomic loci, but only regulates hundreds genes. Genome‐wide chromatin interaction studies revealed proximal promotor various GC‐regulated genes interacts with multiple distal enhancer elements harbour GC‐dependent binding. significance such...

Background: Acute allergen exposure is associated with transient epithelial barrier loss in the asthmatic airways, allowing passage of intraluminal allergens, particles, and cytokines to create a positive feedforward loop inflammation.Cytokines lipid signalling molecules (i.e., phospholipids) stimulate inflammatory cascade suggesting that release from immune cells or airway may contribute dysfunction.Here we focus on role lysophosphatidic acid (LPA) dysfunction compare it important Th2...