Evidence that hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of Interleukin-1β(1L-1β)in astrocyte cultures
Bibliographic record
Abstract
Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor composed of HIF-1α and HIF-1β subunits and involved in the regulation of gene expression in adaptive response to hypoxia. This study reports that the inflammatory cytokine interleukin-1β (IL-1β) shares common features of other known HIF-1α-regulated genes. Both human and mouse IL-1β genes carry multiple HIF-1-binding sites in their promoter regions and are up-regulated by hypoxia and CoCl2 in human and mouse astrocytes in parallel with up-regulation of HIF-1α mRNA and protein. Inhibition of HIF-1α degradation by proteasome inhibitor, MG-132, potentiated hypoxia-induced IL-1β release from human astrocytes, and this response was blocked in the presence of CdCl2. Mouse astrocytes with Hif1α+/− genotype demonstrated attenuated up-regulation of both HIF-1α and IL-1β by hypoxia and CoCl2. Mutation of HIF-1-binding sites in the IL-1β promoter abolished hypoxia-induced transactivation of the reporter gene transfected into human astrocytes. Similarly, HIF-1 binding “decoy” oligonuleotide transfected into astrocytes inhibited both hypoxia-induced transactivation of the HIF-1 reporter gene and IL-1β secretion from transfected astrocytes. Collectively, the evidence suggests that the transcriptional activation of IL-1β in astrocytes exposed to hypoxia occurs via HIF-1.
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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".