Catalase inhibition can modulate the ability of peripheral blood T cells to undergo apoptosis in Crohn's disease.

Crohn's disease (CD) is a chronic relapsing inflammatory disorder in which defective apoptosis of mucosal T cells is postulated to produce sustained inflammation and reactive oxygen species accumulation. Whether CD T cells are intrinsically resistant to apoptosis or whether this resistance is acquired at the intestinal site needs to be clarified, as the cellular mechanisms modulate the impaired apoptosis in these cells. Here, we analysed peripheral blood T cells from patients naïve to specific CD treatment at the onset and from healthy controls. Non-activated freshly purified lymphocytes were cultured and submitted to in vitro protocols for activation (CD3/CD28 antibodies) and apoptosis (Fas antibody). Cells were analysed by flow cytometry. Caspases (3, 8, and 9) and catalase activity were measured; protein levels of bax, Bcl-2, and NF-kB were detected by western blotting, and cytokines by Luminex-based assays. The results showed that CD4 T cells from CD patients are less prone to apoptosis before they can migrate to the intestinal mucosa. Caspase-9, FasR, sIL-2Rα, IL-17A, IFNγ, IL-6, TNF-α, and IL-10 were shown to be significantly different in CD but not for the rest of the analysed biological elements. Catalase activity was significantly reduced in CD T cells, which was confirmed in ex vivo experiments in which catalase inhibition in T cells from healthy controls triggered apoptosis inhibition in a dose-dependent manner. In conclusion, apoptosis inhibition of CD T cells is a feature of these cells before they can migrate to the intestinal mucosa. Noteworthy, the impaired apoptosis of T cells can be directly influenced by catalase inhibition.

Estrés oxidativo en la enfermedad de Crohn / Oxidative stress in Crohn's disease

La enfermedad de Crohn (EC) se caracteriza por dar lugar a procesos de inflamación transmural que con mayor frecuencia se localizan en la región del íleon terminal. Aunque los mecanismos fisiopatológicos de la enfermedad no están todavía bien definidos, se ha observado que la respuesta inmunitaria no regulada está asociada a una producción elevada de especies reactivas de oxígeno (ERO). Estos elementos están relacionados con unos sistemas complejos denominados defensas antioxidantes (DAO) que tienen la función de regular los ERO, evitando así sus efectos dañinos. Sin embargo, se ha descrito ampliamente para la EC la presencia de un desequilibrio entre la producción de ERO y su eliminación por los elementos antioxidantes, originando lo que se denomina estrés oxidativo. Enmarcado en este contexto, a continuación se profundiza sobre los hallazgos más destacados relacionados con el estrés oxidativo en la mucosa intestinal y en la sangre periférica (AU)

Crohn’s disease (CD) is characterized by transmural inflammation that is most frequently located in the region of the terminal ileum. Although the physiopathological mechanisms of the disease are not yet well defined, the unregulated immune response is associated with high production of reactive oxygen species (ROS). These elements are associated with complex systems known as antioxidant defenses, whose function is ROS regulation, thereby preventing the harmful effects of these elements. However, the presence of an imbalance between ROS production and ROS elimination by antioxidants has been widely described and leads to oxidative stress. In this article, we describe the most significant findings on oxidative stress in the intestinal mucosa and peripheral blood