Role of Specific CCAAT/Enhancer-binding Protein Isoforms in Intestinal Epithelial Cells
Bibliographic record
Abstract
Intestinal epithelial cells participate in the acute phase response in response to inflammation. We have shown that acute phase protein genes are induced during intestinal acute phase response, and that the CCAAT/enhancer binding protein family of transcription factors are involved. To address the role of specific C/EBP isoforms, we generated IEC-6 rat intestinal epithelial cell lines expressing different C/EBP isoforms, by retroviral infection. Overexpression of C/EBPalpha p30 and C/EBPdelta led to increases in C/EBPbeta LAP and C/EBPbeta LIP endogenous protein levels, as determined by electrophoretic mobility shift assays and Western blot. Inhibition of C/EBP activity with dominant negative C/EBPs (C/EBPbeta LIP, 3hF, 4hF) decreased glucocorticoid-, cAMP- and IL-1 responsiveness of the endogenous haptoglobin gene, while overexpression of each C/EBP isoform increased the responsiveness to these regulators. In contrast, dominant negative C/EBPs or C/EBP isoforms did not alter the expression of alpha-acid glycoprotein in response to dexamethasone and of C/EBPbeta and C/EBPdelta in response to various regulators as assessed by Northern blot. These data show that the three C/EBP isoforms are involved in the regulation of haptoglobin and that C/EBPbeta, C/EBPdelta, and alpha-acid glycoprotein expression are not induced by C/EBP isoforms in contrast to other cell types. C/EBPbeta LAP-expressing cells showed an inhibition of cell growth characterized by a delay in p27(Kip1) decrease in response to serum and a decrease in cyclin D isoforms and cyclin E protein levels. Finally, C/EBP isoforms interact with the E2F4 transcription factor. Thus, specific C/EBP isoforms are involved in the differential expression of acute phase protein genes in response to hormones and cytokines. Furthermore, C/EBP isoforms may play a role in the control of cell cycle progression.
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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 | 0.001 |
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".