CHAPITRE V: Reporter Gene Analysis of Human ALOX5 Promoter Polymorphisms
6.5 En conclusion
Cette thèse a mis en évidence l’importance d’élucider les mécanismes qui régulent non seulement l’expression de la 5-LO et la biosynthèse des LT, mais aussi l’activité
des métabolites produites suite à la dégradation du LTB4. D’abord, les résultats
présentés dans cette thèse démontrent que les métabolites du LTB4 réduisent les
les molécules importantes pour la résolution de l’inflammation. Il faudrait aussi voir
si les métabolites du LTB4 participent également à ce processus important du
système immunitaire. L’effet du 20-OH- et du 20-COOH-LTB4 peut expliquer la
susceptibilité aux infections des patients atteints de fibrose kystique et conséquemment l’inhibition de leur synthèse pourrait s’avérer une cible thérapeutique potentielle. Ensuite, nous avons démontré pour la première fois que le promoteur ALOX5 peut être activé par un agoniste physiologique comme le LPS. Ce résultat nous permet de mieux comprendre comment la maturation des monocytes peut induire la 5-LO et la biosynthèse des LT à la suite d’une infection bactérienne. Finalement, dans le cas des maladies cardiovasculaires, nos résultats n’expliquent pas l’association nutrigénétique précédemment observée. D’ailleurs une meilleure compréhension des mécanismes impliqués pourrait aider le dépistage des personnes prédisposées à l’athérosclérose, et en conséquence, fournir les outils nécessaires pour la prévention de la maladie incluant des interventions nutritionnelles ciblées.
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