A48 COLITIS FAVORS THE EXPANSION OF BACTERIA THAT ACTIVATE PAR2 AMPLIFYING INFLAMMATORY RESPONSE
Notice bibliographique
Résumé
Abstract Background Proteolytic imbalance has been described in patients with inflammatory bowel disease (IBD) and in different models of experimental colitis. Although the proteases reported to be increased are mainly from the host, the role of bacterial proteases has recently emerged, as they can promote inflammation, in part, through activation of Protease-activated receptors (PARs). PAR2 deficient mice are resistant to inflammation and PAR2 activation affects multiple aspects of the tissue response to injury. However, PAR2 communicates with other receptors such as toll-like and other PARs, which are important in multiple immune signaling pathways. Thus, the direct implication of PAR2 in colitis, and specifically the activation of the external domain by microbial proteases, remains unclear. Aims To study the role of PAR2 and bacterial proteases in experimental colitis. Methods C57BL/6 and protease-resistant PAR2 (R38E-PAR2) mice, in which activation site of PAR2 is missing, were given 3.5% dextran sodium sulfate (DSS) in drinking water for 5 days followed by 2 days of water. Control C57BL/6 (wild-type) and R38E-PAR2 mice received only water. Percent weight change was evaluated along the study. Fecal microbiota (16S Ilumina), expression of proinflammatory genes (Nanostring), gut permeability (Ussing chamber), proteolytic activities (colorimetric assay) and bacterial translocation (plating) were measured in all mice at sacrifice. Inflammation was determined by analyzing stool consistency, fecal blood and by microscopic scores (Cooper score). Bacteria with proteolytic activity were isolated using agar-media with protein as main nutrient and bacterial capacity to release the external domain of PAR2 was tested in cells harbouring luciferase at the PAR2 N terminus. Results Wild-type, but not R38E-PAR2 mice, had increased expression of several pro-inflammatory genes, such as tnf, map3k and tlr, gut dysfunction and increased intestinal permeability, increased bacterial translocation into spleen and altered microbiota profiles following DSS treatment. DSS induced colitis in both mouse strains, but clinical and microscopic scores were significantly lower in R38E-PAR2 compared with wild-type mice. DSS increased the abundance of opportunistic pathogens such as Enterococcus and Staphylococcus only in wild-type mice. Proteolytic phenotype of these bacteria, and their capacity to cleave the external domain of PAR2, was confirmed. Conclusions Mice lacking the activation site of PAR2 are protected from DSS-induced colitis. DSS treatment leads to expansion of bacteria releasing active proteases, which may mediate injury through PAR2. These results suggest that intestinal injury promotes microbial proteolytic imbalance which in turn, exacerbates inflammation. Funding Agencies CAG, CCC, CIHR
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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 0,001 |
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 ».