Cytotoxic Mechanism of FK506 on Human T Lymphocytes

PURPOSE: FK506 (Tacrolimus) has been widely used as an immunosuppressant. We examined the effects of FK506 on the activation, proliferation and expression of cytotoxic effector molecules of Jurkat human T-lymphocytes. METHODS: We investigated the effects of this compound on cell viability, the production of reactive oxygen species and mitochondrial dysfunction. The cells were cultured in the presence or absence of FK506. Flow cytometric analysis was performed after staining with PI. The viability of the Jurkat cells was decreased by the addition of FK506 in a dose-and time-dependent manners. RESULTS: FK506-induced cytotoxicity was characterized by G0/G1 phase cell-cycle arrest. FK506 induced cell death was confirmed by the caspase-3 protease activation. In addition, the pharmacologic scavenging study of reactive oxygen species (ROS), including H2O2, revealed that cytotoxicity was achieved by the generation of ROS, which might modulate the mitochondrial dysfunction. CONCLUSION: These results suggest that FK506 functions in CDK4-cyclin D1 mediated cell-cycle arrest of Jurkat cells via generation of ROS and mitochondrial dysfunction.

A case of pericardial actinomycosis with acute myocardial infarction and cerebral infarction: mimicking pericardial tuberculosis / 대한내과학회지

Actinomycosis infection can involve most part of the human body including mouth, cervicoface, chest, abdomen and pelvis. Cardiac involvement occurs in less than 2 percent of the infection of actinomyces israelii and pericardial involvement is rare. 34 year male was admitted because of chest pain and general weakness for several months. Echocardiography revealed akinesia of apex suggesting myocardial infarction and large pericardial effusion. Under the impression of pericardial effusion from tuberculosis infection, the patient was started on anti-tuberculosis medicine. Pericardial window operation with pericardial biopsy was performed 7 days later when the patient failed to show a significant improvement. Pericardial biopsy confirmed actinomycosis infection. During admission, the patient had a cerebral infarction with left hemiparesis. The patient was treated with high dose penicillin and improved symptomatically. Echocardiography showed resolution of pericardial effusion.