P085 The effect of vitamin D on macrophage function and polarization in Crohn's disease
Notice bibliographique
Résumé
Background: Defective bacterial clearance by macrophages is believed to play an important role in Crohn's disease (CD). Phenotypes of macrophages include inflammatory M1 and anti-inflammatory M2. Vitamin D has been shown to reduce colitis severity but the mechanisms remain unclear. The effect of Vitamin D on M1 and M2 macrophages in IBD has not been investigated. The aim was to identify possible differences in M1 and M2 macrophages between CD patients and controls and to determine the effect of 1,25 vit D on macrophage function and phenotype markers. Methods: PBMC were isolated from peripheral blood of 45 CD patients and 33 controls not taking vitamin D supplements. REB approval and patient consent was obtained. Monocytes were isolated using CD14 microbeads. M1 and M2 type macrophages were generated by culturing of monocytes in the presence of GM-CSF and M-CSF, respectively. Cytokines were determined by ELISA following stimulation with 100 ng/ml LPS. Phagocytosis was determined by measuring the uptake of FITC-latex beads using flow cytometry. Chemotaxis assays were performed in transwell plates. Expression of M1 and M2 markers was determined by qPCR. Results: No difference in chemotaxis or phagocytosis was observed in CD macrophages compared to controls. M2 displayed greater phagocytic activity than M1 (94.6% vs 80.3%). Phagocytosis was not altered after treatment with 1,25D. M1 migrated in slightly higher numbers toward CCL2 and fMLP compared to M2. Vit D slightly increased migration of both types toward fMLP (+18–26%). LPS-induced production of TNFα, IL-12p40 and IL-10 was comparable between macrophages in CD and controls. M1 produced higher amounts of IL-12p40 and TNFα compared to M2 (p<0.0005 and p<0.05, respectively) whereas IL-10 production was greater in M2 (1566 vs 152 pg/ml, p<0.005). Preincubation with 1,25D greatly decreased IL-12p40 production by M1 (-64.9%, p<0.0005) as well as that by M2 (-100%, p<0.05). 1,25D also decreased TNFα production by M1 (-49.6%, p<0.05) and IL-10 by M2 (-28.2%, p<0.05). M2 macrophages preferentially express F13A1, PTGS2, CD163, CXCL10, CD14 and MMP2, whereas TGFβ, CCL1 and CYP27B1 expression was higher in M1. Marker expression was similar between CD and control macrophages. M1 and M2 markers were not differentially modulated by vit D. Conclusions: Peripheral blood derived macrophage chemotaxis and phagocytosis in CD is similar to those from controls. The main effect of 1,25D was to markedly decrease pro-inflammatory cytokine production from M1 macrophages. However, 1,25D did not modulate macrophage polarization to the anti-inflammatory M2 phenotype. This study was supported by a grant from the Dairy Farmers of Canada.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».