Enhancement of inflammatory mediator release by β<sub>2</sub>‐adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: Due to their potent bronchodilator properties, beta(2)-adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of beta(2)-adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of beta(2)-adrenoceptor agonists on inflammatory mediator release. EXPERIMENTAL APPROACH: Transcription factor activation, and both release and mRNA expression of IL-6 and IL-8 were examined by luciferase reporter assay, elisa and real-time RT-PCR in bronchial human epithelial BEAS-2B cells or primary human bronchial epithelial cells grown at an air-liquid interface. KEY RESULTS: Pre-incubation with beta(2)-adrenoceptor agonists (salbutamol, salmeterol, formoterol) augmented the release and mRNA expression of IL-6 and IL-8 induced by IL-1beta and IL-1beta plus histamine, whereas NF-kappaB-dependent transcription was significantly repressed, and AP-1-dependent transcription was unaffected. These effects were mimicked by other cAMP-elevating agents (PGE(2), forskolin). Enhancement of cytokine release by beta(2)-adrenoceptor agonists also occurred in primary bronchial epithelial cells. Addition of dexamethasone with salmeterol repressed IL-6 and IL-8 release to levels that were similar to the repression achieved in the absence of salmeterol. IL-6 release was enhanced when salmeterol was added before, concurrently or after IL-1beta plus histamine stimulation, whereas IL-8 release was only enhanced by salmeterol addition prior to stimulation. CONCLUSIONS AND IMPLICATIONS: Enhancement of IL-6 and IL-8 release may contribute to the deleterious effects of beta(2)-adrenoceptor agonists in asthma. As increased inflammatory mediator expression is prevented by the addition of glucocorticoid to the beta(2)-adrenoceptor, our data provide further mechanistic support for the use of combination therapies in asthma management.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".