IL‐1β signalling in glial cells in wildtype and IL‐1RI deficient mice
Bibliographic record
Abstract
1. Interleukin-1 (IL-1) has been implicated in neurodegeneration and in central nervous system (CNS)-mediated host defence responses to inflammation. All actions of IL-1 identified to date appear to be mediated through its only known functional type I receptor (IL-1RI). However, our recent evidence suggests that some actions of IL-1 in the brain may be IL-1RI independent, suggesting the involvement of a new, hitherto unknown functional receptor for IL-1. 2. The objective of the present study was to determine if primary mixed glial cells express additional functional IL-1 receptors by studying the signalling mechanisms responsible for the pro-inflammatory actions of IL-1beta in cultures derived from IL-1RI-/- and wildtype mice, and to characterize the functional importance of IL-1 signalling pathways in glia. 3. IL-1beta induced marked release of IL-6 and prostaglandin-E(2) (PGE(2)) in the culture medium, and activated nuclear factor-kappa B (NFkappaB) and the mitogen-activated protein kinases (MAPK) p38, c-Jun N-terminal kinase (JNK) and the extracellular signal-regulated protein kinase (ERK1/2) in cells from wildtype mice. These responses were dependent on IL-1RI, since cells isolated from IL-1R1-/- mice did not demonstrate any of these responses. 4. In wildtype mice, inhibition of p38 or ERK1/2 MAPKs significantly reduced IL-1beta induced IL-6 release, whilst the NFkappaB inhibitor caffeic acid phenethyl ester (CAPE) modulated IL-1 induced IL-6 release by action on NFkappaB and MAPKs pathways. 5. These data demonstrate that IL-1RI is essential for IL-1beta signalling in cultured mixed glial cells. Thus IL-1 actions observed in IL-1RI-/- mice in vivo may occur via an alternative pathway and/or via different CNS cells.
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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 | 0.001 |
| 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 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".