A85 SEMAPHORIN-3E AMELIORATES INTESTINAL INFLAMMATION BY REGULATING EXPRESSION OF TIGHT JUNCTION PROTEIN AND PROINFLAMMATORY MEDIATORS
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Notice bibliographique
Résumé
Ulcerative colitis (UC) is characterized by an alterations of tight junction (TJ) barrier and immune responses that result in abnormal passages of exogenous antigens such as gut-derived bacterial lipopolysaccharides (LPS). Semaphorin-3E (Sema3E) and its receptor plexin D1 (PLXD1R) are key regulators of epithelia and immune systems To investigate Sema3E activity in human and animal model of colitis and its effects on the intestinal epithelial cell functions Sema3E mRNA level and its correlation with TJ proteins and mucosal healing mediator (Krupple-Like Factor [KLF]-5) were quantified in human rectal biopsies. PLXD1R expression was quantified by immunofluorescence/RT-qPCR in Caco2 epithelial cell line and mice colonic tissues. Proliferation, metabolism, viability and wound healing properties were evaluated after 24 hours of treatment with Sema3E recombinant protein (100ng/ml). TJ proteins and KLF-5 were quantified by RT-qPCR in Caco-2 cells pretreated with Sema3E for 24 h and challenged with LPS (1μg/ml) for additional 24 h. Dextran sulfate sodium (DSS)-colitis was induced in BL6/57 mice for 5 days. Sema3E treatment (10µg/kg/day/intra-peritoneal) started at day 5 after induction of colitis and lasted for 4 days. Disease activity index (DAI), macroscopic and histological scores were assessed. mRNA and protein levels of pro-inflammatory cytokines and KLF5 were quantified. Sema3E is reduced in active and mild UC patients and has strong positive correlation with CLDN1 (r = 0.54, P =0.03), ZO-1 (r = 0.53, P = 0.03), CADH1 (r = 0.60, P =0.01), OCLDN (r = 0.64, P =0.008), KLF-5 (r = 0.52, P =0.03), TLR2 (r = - 0.6147, P =0.0103) and TLR4 (r = - 0.5794, P =0.0207). PLXD1R is expressed by Caco2 cells and mice colonic tissue. Sema3E accelerated significantly the epithelial cells migration when compared to control group. No significant changes on epithelial cells proliferation, metabolism and viability were detected. Compared to LPS-induced inflammation, Sema3E treatment increased the expression levels of TJ proteins (Cldn1, Zo-1, ECadh1, Ocldn) and Klf5, and decreased Tlr2 without significant changes in Tlr4. Sema3E treatment decreases DAI, macroscopic and histological scores in DSS-induced colitis compared with control. Il6 and Mcp1 were significantly decrease in colitic mice treated with Sema3E when compared to untreated mice. Il1bTnfa tend to decrease whereas Klf5 tends to increase. No changes in colonic levels of Tlr2, Tlr4, Cldn1, Zo-1 and Ocldn were detected. Sema3E regulates intestinal inflammation through epithelial cells barrier markers in human and cell line and reduces experimental inflammation and proinflammatory mediators. These findings may lead to improved therapeutic strategies in the treatment of UC by restoring Sema3E level in UC patients. CCC, CIHR
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Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 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) | 0,000 | 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 découle