Human rhinovirus infection of human bronchial epithelial cells results in migration of human airway smooth muscle cells
Bibliographic record
Abstract
Young children who experience human rhinovirus (HRV)-associated wheezing illnesses are more likely to develop subsequent asthma [ 1 ]. This has led to the hypothesis that HRV infection may be involved in the pathogenesis of airway remodeling in asthma [ 2 ]. Increased airway smooth muscle (ASM) mass, in which ASM cells are in close proximity to the subepithelial region, is a characteristic feature of airway remodeling [ 3 ]. We have shown that HRV infection of human bronchial epithelial (HBE) cells, both in vitro and in vivo , results in the upregulation of airway remodeling mediators [ 4 ]. We now sought to determine whether HRV infection of HBE cells is associated with airway smooth muscle (ASM) chemotaxis. Primary HBE cells pre-treated with medium containing 1% insulin, transferrin, and selenium (ITS) for 24 hours were exposed to medium (control) or purified HRV-16 (MOI: 0.3-1) for 24 hours. HBE cell supernatants were then studied as chemoattractants for ASM chemotaxis. ASM migration was examined using both a 48-well modified Boyden chamber and a 16-well xCELLigence apparatus (Roche, Laval, Canada). In the latter case, migration to HBE supernatants was measured via electrical impedance, as per manufacturer’s instructions, and compared to medium control. Chemotactic gradient was abolished by addition of chemoattractants to top and bottom wells of the apparatuses. Additionally, the effects of filtered supernatants and pre-treatment with Pertussis toxin (PTX) on ASM chemotaxis were studied using the xCELLigence apparatus. Supernatants from HRV-16 infected HBE cells resulted in significantly greater ASM cell directional migration, compared to supernatants from HBE cells exposed to medium (negative control) in both the Boyden chamber (n=3; p<0.01) and the xCELLigence system (n=3; p<0.001); relationship was concentration-dependent (n=3; p<0.05). Time course experiments demonstrated that rate of migration was maximal at 4 hours. Migration was significantly attenuated when the chemotactic gradient was abolished, indicating that directional cell migration is due to chemotaxis and not chemokinesis (n=3; p<0.001). ASM migration significantly increased even after filtration of HRV and proteins greater than 100,000 MW (n=3; p<0.05). However, pretreatment with PTX abrogated HRV-induced ASM chemotaxis (n=3, p<0.05). Pretreatment with dexamethasone, formoterol, or combination, abolished ASM chemotaxis (n=4, p<0.05). These data provide the first demonstration that HRV infection of airway epithelial cells produces soluble factor(s) that cause directional migration of ASM cells. Moreover, migration appears to be dependent on a PTX sensitive pathway. Taken together, they provide further evidence for a 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".