Lung epithelial C/EBPβ is necessary for the integrity of inflammatory responses to cigarette smoke
Bibliographic record
Abstract
CCAAT/enhancer-binding protein-β (C/EBPβ) is a key intracellular regulator of inflammatory signalling; however, its role in pulmonary inflammation is unknown. Therefore, we characterised the role of C/EBPβ in the airway epithelial response to cigarette smoke. mRNA expression in airway epithelium of current, former, and never-smokers, as well as in vitro cigarette smoke extract-treated human airway epithelial cells, were analysed by microarray and real-time PCR, respectively. Mice with lung epithelial-specific inactivation of C/EBPβ (CebpbΔLE) were exposed to cigarette smoke for 4 or 11 days. Lung histology, bronchoalveolar lavage cell differentials, and pulmonary expression of inflammatory and innate immune mediators were assessed. C/EBPβ expression was down-regulated in the airway epithelium of both current and former smokers compared to never-smokers, as well as in cigarette smoke extract-treated human airway epithelial cells. Cigarette smoke-exposed CebpbΔLE mice displayed blunted neutrophil influx, and compromised induction of neutrophil chemoattractants GROα and MIP-1γ, inflammatory cytokines TNFα and IL-1β, and the innate immunity gene SAA3, compared to smoke-exposed controls. Inhibition of C/EBPβ in human airway cells in vitro caused similarly compromised response to cigarette smoke extract. In summary, this suggests a previously unknown role for C/EBPβ and the airway epithelium in mediating inflammatory and innate immune responses to cigarette smoke.
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How this classification was reachedexpand
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 | 0.007 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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 teacher head, 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".