Glucocorticoid-induced transcriptional regulators in human airway cells and airways
Why this work is in the frame
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Bibliographic record
Abstract
<b>Introduction:</b> Inhaled glucocorticoids (corticosteroids) act on the glucocorticoid receptor (GR, NR3C1) to control inflammation in asthma by reducing the expression of inflammatory genes. This may involve direct repression of inflammatory gene transcription by GR and induction of anti-inflammatory genes. However, GR is a transcription factor that induces the expression of many genes, including other transcription factors. <b>Aims:</b> To characterize the expression of transcriptional regulators that are induced by glucocorticoids in airway epithelial cells and in the airways. <b>Methods:</b> Gene expression profiling of RNA from: i) primary human bronchial epithelial cells; ii) pulmonary A549 epithelial cells; and iii) BEAS-2B cells following budesonide treatment was performed using Affymetrix PrimeView microarrays. Data was compared to that from biopsies of healthy individuals 6 h following a single dose of inhaled budesonide. Selected genes were validated by qPCR. <b>Results:</b> Gene ontology showed up to 20% of genes upregulated by budesonide treatment in the human airways as being involved in transcription control and many of these were common with the epithelial cells. Expression of CEBPD, FOXO3, HIF3A, KLF9, KLF15, PER1, TFCP2L1, TSC22D3 and ZBTB16 were significantly upregulated in the biopsy samples and in HBE cells, with some variability between A549 and BEAS-2B, or other structural cells. <b>Conclusion:</b> The large number of transcriptional regulators induced by glucocorticoids indicates key roles in mediating downstream responses. Mechanistic studies are required to identify roles for these factors in the desirable therapeutic effects and/or unwanted side effects of glucocorticoids.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 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 it