Effect of exogenous ceramide on barrier function of human airway epithelial cells
Bibliographic record
Abstract
Maintaining the integrity of the airway epithelial barrier is essential in preventing increased permeability to harmful molecules and pathogens, which may lead to increased risk of developing respiratory infection and disease. We have previously shown that in human airway epithelial cells metformin increases tight junction (TJ) assembly after pathogen disruption by promoting the abundance and assembly of full length occludin, and that this process involves phosphorylation of occludin via an AMPK‐PKCζ pathway. During bacterial infection alpha toxin activates the acid sphingomyelinase/ceramide system which can cleave membrane proteins releasing ceramide to form ceramide rich domains, this signals the reorganization of receptors and activation of protein kinase C isoforms such as PKCζ. This study aimed to investigate the effect of N ‐Palmitoyl‐d‐erythro‐sphingosine (C16:0 ceramide) on epithelial integrity of human airway epithelial cells (H441 cells). TJ assembly was measured after calcium switch assay by measuring the transepithelial electrical resistance (TEER) and paracellular transport of sodium‐fluorescein which was used as an index of permeability (P app ) in the presence of 0.1 μM or 1 μM ceramide. We found that after 24h there was 11% change in TEER (138 ± 15 vs 125 ± 14 Ω/cm 2 , P = 0.34; n=8) and 10% change in P app (16 ± 6 vs 18 ± 7 cm/s x 10 −6 , P = 0.19; n=3) with 0.1 μM ceramide compared to control. No changes were observed with 1 μM ceramide. Immunofluorescence staining for occludin, claudin‐1 or claudin‐3 did not show a difference in localisation with ceramide treatment compared to control untreated cells. These results indicate so far that in airway epithelial cells activation of PKCζ by ceramide only evokes a minor effect on tight junction reassembly or permeability. Support or Funding Information AstraZeneca R&D This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.001 | 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".