Growth factors regulate proteinase activated receptor – 2 (PAR-2) on airway epithelium
Bibliographic record
Abstract
Many aeroallergens activate PAR-2 receptors on the airway epithelium. We have shown that PAR-2 activation participates in allergic sensitization and allergic airway inflammation in animal models of asthma. Moreover, PAR-2 is upregulated on the airway epithelium of asthmatics, but the mechanisms and factors responsible are unknown. As asthmatic airways are under various types of physiological stress, we hypothesized that cellular stress upregulates PAR-2 on airway epithelium and this upregulation is functional. Human bronchial epithelial cells were cultured with or without growth factors for 24hrs/48hrs and PAR-2 mRNA levels were studied by qRT-PCR. PAR-2 functions were assessed by measuring PAR-2-mediated calcium release from intracellular stores into the cytoplasm and IL-8 release in supernatants. We have previously shown that growth factor deprivation, but not oxidative stress or hypoxia, significantly upregulates PAR-2 mRNA in normal bronchial epithelial cells. We now show that growth factor deprivation also induces PAR-2 upregulation in airway epithelial cells from asthmatic individuals (2.1 +/- 0.1 fold, n=2); this upregulation was reversible upon growth factor addition. We omitted individual growth factor from the culture media. Omission of only insulin caused significant PAR-2 mRNA upregulation (1.6 +/- 0.1 fold, n=4). In addition, supplementation of stressed cells with insulin reversed the growth factor deprivation-induced PAR-2 upregulation (n=3). PAR-2-mediated activation of stressed cells induced more calcium release from internal stores and higher release of the inflammatory mediator IL-8 (2.1 +/- 0.2 fold, n=6) compared to non-stressed cells. Growth factor deficiency could be the driving force for PAR-2 upregulation in asthmatic airways. Insulin may be one of the growth factors that regulate PAR-2 transcription. In conditions of growth factor deprivation, PAR-2 upregulation may lead to increased activation of airway epithelial cells resulting in the higher release of pro-inflammatory mediators. Therefore, understanding PAR-2 regulation may allow the development of new anti-inflammatory approaches for airways diseases.
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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 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".