Papel funcional do triterpeno natural friedelina sobre células epiteliais tímicas senescentes

Abstract

Thymic involution, essential for T lymphocyte maturation, occurs with aging and results in a decline in immune function. This process is closely related to cellular senescence of thymic epithelial cells (TECs), primarily induced by oxidative stress. The accumulation of oxidative damage in TECs compromises their function and contributes to thymic microenvironment degeneration. Friedelin, a triterpene with antioxidant and anti-inflammatory properties, shows potential to modulate TEC biology and combat senescence. Based on these arguments, the present work investigated the effects of friedelin on murine TECs under normal and senescent conditions. Murine TECs from the 2BH4 cell line were cultured under different conditions: control (untreated), treated with friedelin (0.1 and 1 μM), and subjected to D-galactose-induced senescence (40 mg/mL), with or without friedelin treatment. Cell viability, proliferation, reactive oxygen species (ROS) production, and p16 senescence marker expression were evaluated by PCR. Laminin and fibronectin production were assessed by immunofluorescence. TEC function was evaluated through thymocyte adhesion and survival assays. Friedelin did not exhibit toxicity towards TECs at the tested concentrations. In non-senescent cells, friedelin increased laminin production and promoted thymocyte adhesion, particularly doublepositive (CD4+CD8+) and single-positive (CD4+) cells. However, friedelin did not reverse D-galactose-induced senescence, characterized by reduced cell proliferation, increased ROS, and p16 expression. In co-culture with senescent TECs, friedelin did not significantly alter thymocyte adhesion or survival. The results of this study demonstrate that friedelin has potential to modulate TEC biology, increasing laminin production and thymocyte adhesion, which may benefit the thymic function. However, in the experimental model of senescence used in this work, friedelin did not reverse oxidative stress-induced senescence. Further studies are needed to elucidate the mechanisms of friedelin action and its therapeutic potential in the context of thymic involution and aging, including the investigation of different doses, administration routes, and combinations with other bioactive compounds.