1. Tacrolimus (FK506) has protective actions against murine bleomycin-induced acute lung injuries
- Author
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Yoshitaka Ohkubo, Seitaro Mutoh, Tadatsura Koshika, Akitoshi Ishizaka, and Yoshitaka Hirayama
- Subjects
Lung Diseases ,medicine.medical_specialty ,Apoptosis ,chemical and pharmacologic phenomena ,DNA Fragmentation ,Lung injury ,Bleomycin ,Dexamethasone ,Tacrolimus ,Mice ,chemistry.chemical_compound ,Cyclosporin a ,Internal medicine ,In Situ Nick-End Labeling ,medicine ,Animals ,Lung ,Pharmacology ,Dose-Response Relationship, Drug ,business.industry ,Respiratory disease ,respiratory system ,Ciclosporin ,medicine.disease ,Specific Pathogen-Free Organisms ,respiratory tract diseases ,Mice, Inbred C57BL ,Survival Rate ,surgical procedures, operative ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Acute Disease ,Female ,Chemokines ,business ,Bronchoalveolar Lavage Fluid ,Immunosuppressive Agents ,medicine.drug - Abstract
The effects of tacrolimus on murine acute lung injury were tested, especially in comparison to dexamethasone. Acute lung injury was induced by intratracheal instillation of bleomycin. Oral tacrolimus significantly improved survival rates of bleomycin-exposed mice, while cyclosporin A or dexamethasone did not. After instillation of bleomycin (day 0), a migration of neutrophils into alveolar spaces peaked on day 3, with concomitant increases of chemokines. On day 6, marked morphological changes in the lungs were observed. All these changes were significantly inhibited by tacrolimus. Furthermore, DNA ladder and immunohistochemical analyses of lungs showed that apoptosis of lung cells appeared on day 6 and was abolished only by the treatment of tacrolimus. These results suggest that both anti-inflammatory and anti-apoptotic action of tacrolimus contribute to improvement of bleomycin-induced acute lung injury.
- Published
- 2005