Engagement of NOD2 has a dual effect on proIL‐1β mRNA transcription and secretion of bioactive IL‐1β
Bibliographic record
Abstract
Synthesis and release of pro-inflammatory cytokines, such as IL-1beta, play a crucial role in the intestinal inflammation that characterizes Crohn's disease. Mutations in the nucleotide oligomerization domain 2 (NOD2) gene are associated with an increased risk of Crohn's disease. Although it is known that NOD2 mediates cytokine responses to muramyl dipeptide (MDP), it is yet unclear whether NOD2 stimulation mediates only transcription of pro-IL-1beta mRNA, or whether NOD2 is also involved in the activation of caspase-1 and release of active IL-1beta. By investigating the response of MNC from Crohn's disease patients homozygous for the 3020insC NOD2 mutation, we were able to show that NOD2 signaling after stimulation with MDP has a dual effect by activating proIL-1beta mRNA transcription and inducing release of bioactive IL-1beta. Because NOD2 engagement amplifies TLR stimulation, we investigated whether activation of caspase-1 by MDP is involved in the NOD2/TLR synergism. The synergy in IL-1beta production between NOD2 and TLR is mediated at post-translational level in a caspase-1-dependent manner, which indirectly suggests that NOD2 also induces caspase-1 activation. In contrast, the synergy in TNF-alpha production after stimulation with MDP and LPS is induced at transcriptional level. This demonstrates that both caspase-1-dependent and -independent mechanisms are involved in the synergy between NOD2 and TLR.
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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 | 0.002 | 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".