Altered Inhibitory κB Alpha Expression in LPS-Stimulated Alveolar Macrophages Following Resuscitated Hemorrhagic Shock
Bibliographic record
Abstract
Patients resuscitated from hemorrhagic shock are at increased risk for the development of organ dysfunction, particularly acute respiratory distress syndrome. The "two-hit hypothesis" wherein shock/resuscitation (S/R) renders the immune system more responsive to subsequent inflammatory stimuli has been suggested as a major mechanism contributing to organ injury. Previous work has shown that S/R primes alveolar macrophages for increased nuclear factor κB (NF-κB) translocation in response to LPS, culminating in increased lung cytokine and chemokine production. Inhibitory κB (IκB) is known to be an important regulator of NF-κB activity. In this article, we investigated the effect of S/R on regulation of IκBα expression in response to LPS both in vitro and in vivo. Two discrete effects on IκB regulation were observed after S/R, which served to augment NF-κB activity. First, antecedent exposure of alveolar macrophages to S/R resulted in increased LPS-induced IκBα degradation through activation of upstream signaling, an effect that resulted in increased NF-κB translocation and cytokine-induced neutrophil chemoattractant gene expression. Second, cells recovered from rodents after S/R had reduced levels of IκB mRNA in response to LPS compared with sham/LPS treatment. This effect was primarily due to the ability of S/R to reverse the prolongation of IκB mRNA stability observed after LPS-alone treatment. Together, these effects on the important regulatory molecule IκB in the macrophage may contribute to the heightened inflammatory response observed after S/R.
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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) | 0.001 | 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".