A156 A HELMINTH EXTRACT DOES NOT ALTER THE ABILITY OF HUMAN IL-4 STIMULATED MACROPHAGES TO ENHANCE EPITHELIAL WOUND REPAIR
Bibliographic record
Abstract
Infection with parasitic helminths can reduce inflammation in animal models of colitis. A component of this anti-inflammatory effect may be induction of IL-4 driven anti-inflammatory/pro-resolution macrophages (M(IL4)) that have been implicated in wound repair. Infection with helminth parasites or exposure to worm extracts may elicit unique macrophage phenotypes. We hypothesized that macrophages co-treated with IL-4 and a crude extract of the rat tapeworm, Hymenolepis diminuta (HdE), would have an enhanced ability to promote repair in wounded epithelial monolayers. To assess the impact of HdE on the development of human and murine M(IL4)s using canonical markers and assess the role of these cells in epithelial wound repair. Human (THP-1 cell line, blood-derived) and murine (bone marrow-derived) macrophages were exposed to IL-4 (10 ng/ml; 48h), HdE (100 mg/ml; 48h), IL4+HdE, or left unstimulated (controls). The expression of M(IL4) markers were assessed by qPCR, immunoblotting or ELISA (human: CD206, CCL18, CD14; murine: arginase-1, Ym1). Caco2 epithelial cells were seeded, grown to confluence in 6-well plates (48h), and wounded with a razor blade. Supernatants collected from the different human macrophage populations were applied and total area of epithelial migration was measured (in mm2) 24h later. TGFb levels in the macrophage supernatants were measured by ELISA. The development of human M(IL4)s was not affected by HdE co-treatment as assessed by any of the markers examined, whereas HdE did reduce protein expression of arginase-1 and Ym1 in murine M(IL4)s (n=4–6). Exposure of wounded epithelial monolayers to supernatants from M(IL4)s increased epithelial migration by 36% ± 14% (n=6, p<0.05) compared to baseline, with HdE neither enhancing nor inhibiting the epithelial wound repair. TGFb levels were increased in M(IL4) supernatants compared to those from non-stimulated macrophages: 353 ± 78* vs. 204 ± 71 pg/ml (n=11; *p<0.05 (paired t test)). HdE has negligible effects on the induction of a human M(IL4) and does not inhibit its ability to promote epithelial wound repair, that could be TGFb-dependent. Thus, (1) M(IL4)s elicited in humans following infection with helminths will not be adversely affected by the release of worm antigen, and (2) if an anti-colitic effect of systemic delivery of helminth antigens to humans results in mobilization of an IL-4-type alternatively activated macrophage, this would be an indirect effect of the worm antigen. CCCNSERC, NSERC HPI CREATE
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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 | 0.001 |
| 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".