Thrombin engages neutrophil-derived secretion products to upregulate interleukin-6 production in atrial cardiomyocytes and the heart
Bibliographic record
Abstract
Abstract Interleukin-6 (IL-6) exerts a highly context-dependent influence on cardiac injury and repair, inflammation and resolution. Thrombin is a dichotomous regulator of these processes in the post-infarcted heart via protease-activated receptors (PAR), particularly neutrophil-expressed PAR4 Cardiomyocytes are an intrinsic source of myocardial IL-6, but it is not known if this can be triggered by thrombin. Here we examined IL-6 production in cardiomyocytes and how this relates to cardiomyocyte-neutrophil cross-talk in the presence of thrombin. In HL-1 cardiomyocytes, thrombin failed to regulate IL-6 expression and secretion, unlike oxidized albumin (oxAlb), an advanced oxidation protein product (AOPP) recognized by CD36 scavenger receptors. Thrombin, however, increased myeloperoxidase (MPO) release and formation of AOPP by human neutrophils in autologous plasma. HL-1 cardiomyocytes exposed to conditioned supernatant from thrombin-stimulated versus control neutrophils displayed higher levels of IL-6 mRNA and greater IL-6 secretion, an effect largely abrogated in the presence of a CD36 inhibitor. In mice with high fat diet (HFD)-induced obesity and cardiometabolic inflammation, myocardial MPO activity and AOPP content were elevated compared to chow-fed mice, together with higher expression of CD36 and IL-6. In conclusion, thrombin evokes neutrophil-dependent oxidation of plasma proteins that can promote cardiomyocyte IL-6 production, likely promoting local inflammation in cardiometabolic disease.
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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 | 0.000 |
| 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 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".