Mechanism of fibroblast inflammatory responses to Pseudomonas aeruginosa elastase
Bibliographic record
Abstract
Receptor tyrosine kinases, including the epidermal growth factor receptors (EGFR), are able to activate the mitogen-activated protein kinases (MAPK) via several adaptor proteins and protein kinases such as Raf. EGFR can be activated by a variety of extracellular stimuli including neutrophil elastase, but we are aware of no report as to whether Pseudomonas aeruginosa produced elastase (PE) could elicit such signalling through EGFR activation. We sought to test the inference that PE modulates inflammatory responses in human lung fibroblasts and that the process occurs by activation of the EGFR/MAPK pathways. We utilized IL-8 cytokine expression as a pathway-specific end point measure of the fibroblast inflammatory response to PE. Western blot analysis was performed to detect phosphorylation of EGFR and signal transduction intermediates. Northern blot, real-time PCR, and ELISA methods were utilized to determine cytokine gene expression levels. We found that PE induces phosphorylation of the EGFR and the extracellular signal-regulated proteins (ERK1/2) of the MAPK pathway, and nuclear translocation of NF-κB. Furthermore, enzymically active PE enhances IL-8 mRNA and protein secretion. Pretreatment of the cells with specific inhibitors of EGFR, MAPK kinase and NF-κB markedly attenuated the PE-induced signal proteins phosphorylation and IL-8 gene expression and protein secretion. Collectively, the data show that PE produced by Pseudomonas aeruginosa can modulate lung inflammation by exploiting the EGFR/ERK signalling cascades and enhancing IL-8 production in the lungs via NF-κB activation.
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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 | 0.000 | 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) | 0.000 | 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".