Down‐regulation of GSTA1 by IL‐1 beta is mediated by overexpression of the transdominant repressor vHNF‐1C
Bibliographic record
Abstract
Interleukin‐1 (IL‐1) beta markedly suppresses glutathione S‐transferase (GST) A1 expression, which has profound implications on protection against cytotoxic byproducts of inflammation. We investigated the role of hepatic nuclear factor 1 (HNF‐1) alpha in the regulation of human GSTA1 by IL‐1 beta in Caco‐2 cells. Overexpression of HNF‐1 alpha increased GSTA1 promoter activity in luciferase reporter assays through a HNF‐1 response element (HRE) in the proximal promoter. IL‐1 beta repressed GSTA1 transcriptional activity in reporter assays but not when the HRE was mutated in luciferase contsructs. Both GST and HNF‐1 alpha mRNA and protein levels progressively increased as cells reached 7 days post‐confluency, however, only GSTA1 mRNA levels were reduced by IL‐1 beta. Overexpression of HNF‐1 alpha failed to counteract IL‐1 beta‐mediated repression of GSTA1 transcription both in reporter assays and at the mRNA level. Moreover, IL‐1 beta had no effect on HNF‐1 alpha binding to the HRE in gel shift assays. Messenger RNA levels of the C isoform of variant HNF‐1 (vHNF‐1C), the transdominant repressor variant form, were 60 fold higher relative to the A and B forms (transcriptional activator forms) in pre‐confluent cells but only 20 fold higher in confluent cells. IL‐1 beta significantly up‐regulated vHNF‐1C expression in pre‐confluent and confluent cells to 80 fold and 30 fold respectively. These findings indicate that IL‐1 beta represses GSTA1 transcription via a mechanism involving overexpression of vHNF‐1C. Supported by the Canadian Institutes for Health Research
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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 | 0.000 | 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) | 0.000 | 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".