Differential synthesis and release of IL-18 and its antagonist, IL-18 binding protein, from human platelets (CCR4P.209)
Bibliographic record
Abstract
Abstract IL-18 is a multifunctional pro-inflammatory cytokine belonging to the IL-1 family. The cytokine is known to be produced from macrophages, dendritic cells, keratinocytes, adrenal cortex etc in the human body. We found that the cytokine as well as its antagonist, IL-18 Binding Protein (IL-18BP), are produced in human platelets. Interestingly, the two of them are synthesized and released differentially from these anuclear cellular elements. Human platelets contain transcripts for the cytokine and synthesize it de novo upon activation as an inactive precursor protein, which is cleaved into mature form by activated caspase 1, whose activation occurs in activated platelets. The platelets continue to release IL-18 over several hours after activation. Freshly isolated resting platelets as well as paraformaldehyde-fixed ones contain very little IL-18. In a sharp contrast to IL-18, its antagonist (IL-18BP) is present pre-made in platelets and is released upon their activation. Platelets contain no transcripts for it and do not synthesize de novo upon activation. Freshly isolated resting platelets as well as paraformaldehyde-fixed platelets contain IL-18BP. Furthermore we found that the two soluble mediators are secreted from platelets via different mechanisms: glyburide inhibits synthesis of active IL-18 but not of IL-18BP from activated human platelets. Our findings bear important implications for a variety human diseases which are accompanied by chronic inflammation.
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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) | 0.002 | 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".