Neonatal Alveolar Type 1 Cells Produce a Pro-inflammatory Response to LPS and TNF-alpha
Bibliographic record
Abstract
Introduction: Bronchopulmonary dysplasia (BPD) is the most common lung disease in premature infants. Inflammation and oxidative stress during the early stages of lung development damage alveolar Type 1 (AT1) and Type 2 (AT2) epithelial cells that line the alveoli, leading to decreased alveolarization and surfactant production. Unlike AT2 cells, the role of AT1 cells in inflammation is not understood. Since inflammation initiates BPD pathogenesis, we sought to characterize the profile of inflammatory markers produced by neonatal AT1 cells in response to lipopolysaccharide (LPS) and tumour necrosis factor α (TNF-α). Methods: AT1 cells were isolated from neonatal rats on postnatal day 4 using fluorescence activated cell sorting. Cells were serum starved for 24hrs and then exposed to LPS (5, 10, 25μg/mL), TNF-α (5, 10, 25ng/mL), or a combination of LPS and TNF-α (10μg/mL and 5ng/mL) for 18h in vitro. Conditioned media was collected for cytokine and chemokine analysis by multiplex ELISA. Results: AT1 cells exposed to both LPS and TNF-α produced a larger inflammatory response than those exposed to LPS or TNF-α alone. After 18h, AT1 cells from the combined LPS and TNF-α group increased the production of IL-6 by 243-fold, CCL2 by 34-fold, and CCL3 by 9-fold in comparison to the control (all p<0.05, n=4). IL-1β and IFN-γ, and the anti-inflammatory cytokines, IL-4 and IL-10, were not detected in any experimental groups at this time point. Conclusion: This is the first study that characterizes the response of neonatal AT1 cells to inflammatory stimuli. Our preliminary findings show that LPS and TNF-α stimulate the production of the pro-inflammatory cytokines and chemokines IL-6, CCL2, and CCL3 in primary AT1 cells. These inflammatory markers are strongly associated with the development of BPD and are predictors of adverse pulmonary outcomes in neonates. Developing therapies that regulate the inflammatory response produced by AT1 cells may be beneficial in mitigating BPD pathogenesis. This work was funded by the Women's Auxiliary of the Hospital for Sick Children. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.004 | 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".