COX-2/PGE₂ signaling drives Toxocara canis-induced lung pathology by enhancing plasminogen activator activity and collagen VI degradation.

Toxocara canis infection induces severe pulmonary pathology, including hemorrhage, inflammation, and extracellular matrix (ECM) degradation, though the underlying mechanisms remain unclear. This study explores the role of cyclooxygenase-2 (COX-2) in lung injury during T. canis infection, focusing on its regulation of plasminogen activator (PA) activity and collagen type VI (COL6) degradation. A murine model was established by orogastric inoculation of 2000 embryonated T. canis eggs. Lung tissues were analyzed via histopathology, ELISA, Western blotting, and immunohistochemistry. COX-2 inhibition with celecoxib was used to assess its effects on COX-2/PGE₂ signaling, PA activity, PI3K/AKT pathway activation, and COL6 degradation. Infection significantly upregulated COX-2, peaking at day 7, correlating with increased PA activity and COL6 cleavage (70/50 kDa fragments). Celecoxib suppressed COX-2/PGE₂, downregulated PI3K/AKT, reduced PA activity, and preserved COL6 integrity, mitigating lung injury. Mechanistically, COX-2/PGE₂ enhances PA activation via PI3K/AKT, exacerbating COL6 degradation. In conclusion, COX-2 drives lung pathology in toxocariasis by modulating PA activity and COL6 degradation, suggesting that targeting COX-2/PGE₂ signaling could ameliorate infection-induced pulmonary damage.