A137 PANCREASTATIN (PTS) EXACERBATES COLONIC INFLAMMATION
Bibliographic record
Abstract
Chromogranin-A (CgA) is elevated in inflammatory bowel disease (IBD) and in murine models of colitis. CgA produced by enteroendocrine cells can be cleaved in several peptides including the immunoregulatory pancreastatin (PTS: CgA273-301). Macrophages (Mo) play a major role in IBD through an impaired transition from a pro-inflammatory (classical activated Mo (CAMs)) to anti-inflammatory (alternative activated Mo (AAMs)) phenotypes. Previously we demonstrated that in mouse, the lack of CgA (CgA-/-) induced a significant decrease of colitis associated to a decreases and an increase of CAM and AAM markers respectively The aim of this study was to investigate the role of PTS in colitis using a pre-clinical and clinical approaches Serum level of PTS and mRNA expression of CgA were quantified in active UC and healthy individuals & mice using ELISA & RT-qPCR. Colitis was induced in CgA-/- and wild type (WT) mice by administrating dextran sulfate sodium in drinking water (DSS 5%, 5 days), and PTS treatment (2.5mg/kg/day, 6 days) or vehicle started 1 day before induction. Disease activity index (DAI) was daily evaluated, and macroscopic scores at sacrifice day. The serum level of CRP was quantified using ELISA. Colonic MPO, IL-1β, IL-6, TNF-α, MIP-1α, MIP-1β, ARG-1, YM1 & TGFβ were assessed using ELISA or RT-qPCR. Naïve peritoneal macrophages were isolated from CgA-/- and WT mice and treated with PTS (200ng/ml; 2, 24h) then exposed for 6 h to LPS (100 ng/ml) or to IL-4/IL-13 (20ng/ml) to promote CAMs or AAMs. CAMs markers (IL-6, IL-1β, TNF-α, MIP-1α, MIP-β) and AAMs markers (ARG-1, YM1, TGFβ) were quantified by using ELISA and/or RT-qPCR. In vitro chemotaxis activity of PTS (200 ng/ml) on naïve Mo was assessed by migration assay using MCP-1 (30ng/ml) CgA & PTS levels significantly increased in human active UC and WT colitic mice. In colitic CgA-/- mice, we confirmed a significant increase of colitis through the regulation of all the pro and anti-inflammatory markers. PTS treatment significantly increased the onset and severity of colitis in CgA-/- and in WT mice. Macroscopic score, CRP, colonic MPO, IL-1β, IL-6, TNF-α, MIP-1α and MIP-1β increased significantly, while ARG-1, YM1, TGFβ decreased in colitic WT & CgA-/- mice treated with PTS. IL-6, IL-1β, TNF-α, MIP-1α & MIP-β were significantly increased in PTS-conditioned CgA-/- CAMs but not in WT, however, a significant decrease of ARG-1, YM1, & TGFβ was demonstrated in both groups. Meanwhile, PTS-conditioned CgA-/- & WT AMS expressed significantly less ARG-1, YM1, & TGFβ when compared to IL-4/IL-13 control condition. In undifferentiated macrophages, PTS significantly increased macrophages migration These findings suggest that PTS contributes to the pathogenesis of colitis and inflammatory process via the modulation of Mo phenotype and function. Targeting PTS may lead to novel therapeutic strategies in IBD CCC, CIHR, NRCResearch Manitoba, Children’s Hospital Research Institute, NSERC
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".