Peroxynitrite mediates cytokine-induced IL-8 gene expression and production by human leukocytes
Bibliographic record
Abstract
Recent studies indicate that nitric oxide (NO) or related compounds may regulate the production of interleukin (IL)-8, a potent proinflammatory chemokine. Here we report that peroxynitrite (ONOO(-)) formed by a reaction of NO with superoxide mediates IL-8 gene expression and IL-8 production in IL-1beta- and TNF-alpha-stimulated human leukocytes in whole blood. The NO synthase inhibitors aminoguanidine and N(G)-nitro-L-arginine methyl ester blocked nuclear accumulation of activator protein-1 (AP-1) and nuclear factor (NF)-kappaB in both polymorphonuclear (PMN) and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by approximately 90% in response to IL-1beta and TNF-alpha. Enhanced ONOO(-) formation was detected in granulocytes, monocytes, and lymphocytes after challenge with IL-1beta or TNF-alpha. The addition of ONOO(-) (0.2-80 microM) to whole blood increased nuclear accumulation of AP-1 and NF-kappaB in PMN and mononuclear leukocytes and augmented IL-8 mRNA expression and IL-8 production in a concentration-dependent fashion. Pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB activation, attenuated approximately 70% of IL-8 release evoked by IL-1beta, TNF-alpha, or ONOO(-). These results indicate that ONOO(-) formation may underlie the action of cytokines towards IL-8 gene expression in human leukocytes.
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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".