Transcriptional and Chromatin Changes Reflect Prolonged Inflammatory Responses to Rhinovirus in Bronchial Epithelial Cells from Adults with Asthma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE152550 | GEO | 2020/10/31
REPOSITORIES: GEO
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Project description:Transcriptional and Chromatin Changes Reflect Prolonged Inflammatory Responses to Rhinovirus in Bronchial Epithelial Cells from Adults with Asthma
| PRJNA642155 | ENA
Project description:There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n?=?9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n?=?9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma.
| S-EPMC7666152 | biostudies-literature
Project description:Rhinovirus (RV) infections trigger asthma exacerbations. Genome-wide expression analysis of RV1A-infected primary bronchial epithelial cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of RV-induced gene expression. Virus replication rates were similar in cells from normal and asthmatic donors. Overall, RV downregulated 975 and upregulated 69 genes. Comparisons of transcriptional profiles generated from microarrays and confirmed by quantitative reverse transcription PCR and cluster analysis showed some up- and downregulated genes in asthma cells involved in immune responses (IL1B, IL1F9, IL24, and IFI44) and airway remodeling (LOXL2, MMP10, FN1). Notably, most of the asthma-related differences in RV-infected cells were also present in the cells before infection. These findings suggest that differences in RV-induced gene expression profiles of cells from normal and mild asthmatic subjects could affect the acute inflammatory response to RV, and subsequent airway repair and remodeling.
| S-EPMC2884103 | biostudies-literature
Project description:Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1?), interleukin-1beta (IL-1?) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1? and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1? and IL-1?, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses.
| S-EPMC3665753 | biostudies-literature
Project description:BACKGROUND:Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS:We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS:ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION:Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.
| S-EPMC5526951 | biostudies-literature
Project description:Human Rhinovirus (HRV) infection can trigger exacerbations of asthma. Understanding of the mechanisms provoking airway inflammation and remodeling in asthma, as well as the pathogenic mechanisms of HRV infection and its association with asthma exacerbations, may offer significant opportunities for improved disease management. Genome-wide expression analysis of HRV type 1A-infected primary bronchial epithelial (PBE) cells from normal and asthmatic donors was performed to determine whether asthma is associated with a unique pattern of gene expression after HRV infection in vitro. Keywords: response to rhinovirus infection
2008-11-01 | GSE13396 | GEO
Project description:Because of its advantage as a minimally invasive procedure, nasal brushings have been increasingly used and proposed as a valuable approach to study lower airway diseases in lieu of bronchial epithelial cells. However, there is limited or conflicting evidence pertaining to whether nasal samples can be surrogates to bronchial samples. The goal of the present study is to test whether nasal epithelial cells have similar antiviral and inflammatory responses to IL-13 treatment and rhinovirus infection, a condition mimicking virally induced asthma exacerbation. Nasal and bronchial airway epithelial cells taken from the same patient were cultured under submerged and air-liquid interface (ALI) culture in the absence or presence of rhinovirus and IL-13 treatment. Inflammatory cytokines IP-10 and eotaxin-3, antiviral gene Mx1 and viral levels were measured.In the absence of IL-13 treatment, nasal and bronchial cells showed a similar IP-10 response in both ALI and submerged cultures. Under the ALI culture, short term (e.g., 3 days) IL-13 treatment had a minimal effect on viral and Mx1 levels in both cell types. However, prolonged (e.g., 14 days) IL-13 treatments in both cell types decreased viral load and Mx1 expression. Under the submerged culture, IL-13 treatment in both cell types has minimal effects on viral load, IP-10 and Mx1. IL-13-induced eotaxin-3 production was similar in both types of cells under either submerged or ALI culture, which was not affected by viral infection.Our data suggest that nasal epithelial cells could serve as a surrogate to bronchial epithelial cells in future studies aimed at defining the role of type 2 cytokine IL-13 in regulating pro-inflammatory and antiviral responses.
| S-EPMC5931947 | biostudies-other
Project description:RationaleThe common cold virus, human rhinovirus (HRV), is the most frequent cause of asthma exacerbations. However, a possible contribution of HRV to the pathogenesis of chronic, persistent asthma has not been defined.ObjectivesTo determine if patients with stable asthma, who are free of clinical signs of a respiratory infection for at least 3 weeks, harbor HRV in their bronchi more frequently than nonasthmatic control subjects, and whether clinical features of asthma are associated with the presence of HRV.MethodsImmunohistochemistry and the indirect in situ reverse transcription-polymerase chain reaction method were used to detect the presence of HRV in bronchial mucosal biopsies in patients with asthma and nonasthmatic control subjects.Measurements and main resultsHRV was found by immunohistochemistry in 9 of 14 bronchial biopsies from subjects with asthma (64.3%) and 2 of 6 nonasthmatic control subjects (33.3%) (P = 0.38). With the more sensitive indirect in situ reverse transcription-polymerase chain reaction method, HRV was found in the mucosal biopsies of 73% of patients with asthma and 22% of nonasthmatic control subjects (P < 0.001). Subjects positive for HRV had lower pulmonary function, higher numbers of blood eosinophils and leukocytes, and eosinophilic infiltration in bronchial mucosa.ConclusionsHRV was detected in the lower airway tissue of patients with asthma significantly more often than in nonasthmatic subjects, and its presence was associated with clinical features of more severe disease.
| S-EPMC2383991 | biostudies-literature
Project description:In asthma there are exaggerated rather than impaired innate and adaptive interferon responses in vivo after RV16 infection, which strongly correlate with inflammation and loss of asthma control.
2020-01-06 | GSE106388 | GEO
Project description:Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and validated the transcription factor cAMP-responsive element binding protein (Creb1) and its transcriptional co-activators (Crtc1-3) as targets of miR-17, miR-144, and miR-21. Sec14-like 3 (Sec14l3) - a putative target of Creb1 - was down-regulated in both asthma models and in NHBE cells upon IL13 treatment, while it's expression correlated with ciliated cell development and decreased along with increasing goblet cell metaplasia. Finally, we propose that Creb1/Crtc1-3 and Sec14l3 could be important for early responses of the bronchial epithelium to Th2-stimuli. This study shows that miRNA profiles can be used to identify novel targets that would be overlooked in mRNA based strategies.
| S-EPMC5382551 | biostudies-literature