A43 CHROMOGRANIN-A REGULATES INDIRECTLY EPITHELIAL REPAIR VIA THE ALTERNATIVELY ACTIVATED MACROPHAGES IN COLONIC INFLAMMATORY STATES
Bibliographic record
Abstract
Chromogranin-A (CHGA), alternatively activated macrophages (M2), and intestinal epithelial cells (IECs) play a significant role during the progression of inflammatory bowel disease (IBD) with M2 being able to regulate IECs. Previously, we demonstrated that chromofungin and catestatin, CHGA-derived peptides, regulate epithelial cell dynamics to improve intestinal inflammation through direct effects on thigh junction (TJ) protein and human colonic epithelial cells (Caco2). Surprisingly, in an experimental model of colitis, the lack of CHGA improves colonic inflammation via an upregulation of M2 markers, and, in active UC biopsies M2 markers were decreased and CHGA mRNA expression correlated negatively with them. Here, we investigated the interplay between the lack of CHGA, M2, and IECs in colitis. mRNA expression of CHGA, TJ proteins (Claudin-1 [CLDN1], zonula occludens-1 [ZO1], occludin [OCLN]), epithelial associated cytokines (IL8, IL18), and collagen (COL1A2) were determined in human colonic tissues and correlation were assessed with CHGA. Acute colitis (5 % DSS, 5 days) was induced in Chga-C57BL/6-deficient (Chga-/-) and wild-type (Chga+/+)mice. Disease activity index (DAI), collagen deposition, colonic TJ proteins, Il-18, Col1a1were determined. Naïve Chga-/-and Chga+/+ peritoneal macrophages were isolated and exposed for 6 h to IL-4/IL-13 (20 ng/ml) to promote an M2 profile. Caco-2 epithelial cells were cultured with Chga-/-and Chga+/+ M2-conditioned medium for 24 h then exposed to 5% DSS for an additional 24 h. Functional properties including proliferation, viability, wound healing were assessed. Compared to healthy individuals, active UC patients demonstrated an increase of CHGA, IL8, IL18, and COL1A2, associated with a decrease of TJ proteins (CLDN1, ZO-1 OCLN). CHGA correlated positively with IL8, IL18, and COL1A2 and negatively with TJ proteins. Deletion of Chga reduced the severity of colitis, colonic collagen deposition, and colonic IL-18, but maintained colonic TJ proteins. We confirmed that M2 polarized Chga-/- macrophages produced more M2 mediators when compared to Chga+/+M2, but here, we demonstrated that Chga-/- M2-conditioned medium protected Caco-2 cells from DSS and oxidative stress injuries by improving Caco-2 cells wound healing, proliferation, viability, by maintaining TJ proteins levels and decreasing the release of IL-8 and IL-18 when compared with Chga+/+ M2-conditioned medium. CHGA indirectly contributes to the development of intestinal inflammation through the regulation of epithelial repair via alternatively activated macrophages. CCC, CIHRCanadian Institutes of Health Research (CIHR) Postdoctoral Fellowship
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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 | 0.000 |
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".