Human rhinovirus infection of human bronchial epithelial cells results in migration of human bronchial fibroblast cells
Bibliographic record
Abstract
Recent studies have demonstrated that structural changes in the airways characteristic of asthma, collectively referred to as airway remodeling, occur in young children even prior to the diagnosis of asthma. Young children who experience human rhinovirus (HRV)-associated wheezing illness within the first three years of life are at increased risk for the subsequent development of asthma. This association, together with evidence that HRV-infected epithelial cells release a number of growth factors and cytokines, has led to the hypothesis that HRV infection may be involved in the pathogenesis of airway remodeling. Thickening of the lamina reticularis found below the true basement membrane in the human airway is a characteristic feature of airway remodeling in asthma. The human bronchial fibroblast (HBF) is believed to contribute to this thickening by moving closer to the laminar reticularis and producing matrix proteins. We hypothesized that HRV infection of human bronchial epithelial (HBE) cells induces production of chemoattractants that can induce HBF migration. Primary HBE cells were grown in bronchial epithelial growth medium (BEGM). Cells were incubated for 2 h in bronchial epithelial basal media (BEBM) prior to experiments. Cells were exposed to BEBM alone (control) or purified HRV-16 (MOI: 1) for 24 hours. HBE cell supernatants from several donors were then recovered, centrifuged, pooled and studied as chemoattractants for HBF chemotaxis. HBF migration was examined using both a 48-well modified Boyden chamber and a 16-well xCELLigence apparatus (ACEA Biosciences, Inc., San Diego, USA). In the latter, migration to HBE supernatants was measured via electrical impedance, as per manufacturer’s instructions, and compared to medium control. Using the xCELLigence system to measure migration in real time, it was found that migration to HBE supernatants and platelet derived growth factor (positive control) was maximal within 6h. Supernatants from HRV-16 infected HBE cells resulted in greater HBF migration compared to supernatants from HBE cells exposed to medium alone (negative control) in both the Boyden chamber and the xCELLigence system. Migration to supernatants from HRV-16 infected cells was concentration dependent. These data provide the first demonstration that HRV infection of HBE produces soluble factor(s) that cause migration of HBF cells. This provides further evidence for a potential role of HRV infection in the pathogenesis of airway remodeling in asthma.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".