The two pore potassium channel <scp>THIK</scp>‐1 regulates <scp>NLRP3</scp> inflammasome activation
Bibliographic record
Abstract
Abstract The NLRP3 (NLR family, pyrin domain containing 3) inflammasome is a multi‐protein complex responsible for the activation of caspase‐1 and the subsequent cleavage and activation of the potent proinflammatory cytokines IL‐1β and IL‐18, and pyroptotic cell death. NLRP3 is implicated as a driver of inflammation in a range of disorders including neurodegenerative diseases, type 2 diabetes, and atherosclerosis. A commonly reported mechanism contributing to NLRP3 inflammasome activation is potassium ion (K + ) efflux across the plasma membrane. Identification of K + channels involved in NLRP3 activation remains incomplete. Here, we investigated the role of the K + channel THIK‐1 in NLRP3 activation. Both pharmacological inhibitors and cells from THIK‐1 knockout (KO) mice were used to assess THIK‐1 contribution to macrophage NLRP3 activation in vitro. Pharmacological inhibition of THIK‐1 inhibited caspase‐1 activation and IL‐1β release from mouse bone‐marrow‐derived macrophages (BMDMs), mixed glia, and microglia in response to NLRP3 agonists. Similarly, BMDMs and microglia from THIK‐1 KO mice had reduced NLRP3‐dependent IL‐1β release in response to P2X7 receptor activation with ATP. Overall, these data suggest that THIK‐1 is a regulator of NLRP3 inflammasome activation in response to ATP and identify THIK‐1 as a potential therapeutic target for inflammatory disease.
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".