Protection against bleomycin-induced lung injury by IL-18 in mice
| Autor: | Haruki Okamura, Atsuo Sekiyama, Akemi Nakatani-Okuda, Haruyasu Ueda, Takakuni Tanizawa, Yukihisa Fujita, Yoshiyuki Tsuji, Susumu Adachi, Shin-ichiro Kashiwamura, Akira Kubota |
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| Rok vydání: | 2005 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Physiology Ratón Pulmonary Fibrosis Lung injury Biology Bleomycin Mice chemistry.chemical_compound Physiology (medical) Pulmonary fibrosis Leukocytes medicine Animals Respiratory system Lung Mice Knockout Antibiotics Antineoplastic Superoxide Dismutase Interleukin-18 Granulocyte-Macrophage Colony-Stimulating Factor Interleukin Lung Injury Cell Biology medicine.disease Interleukin-10 Mice Inbred C57BL Survival Rate Hydroxyproline medicine.anatomical_structure chemistry Mutation Female Interleukin 18 Lung Diseases Interstitial Bronchoalveolar Lavage Fluid |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 289:L280-L287 |
| ISSN: | 1522-1504 1040-0605 |
| Popis: | The role of interleukin (IL)-18 in the protection from interstitial pneumonia and pulmonary fibrosis induced by bleomycin (BLM) was investigated by comparing the severity of BLM-induced lung injuries between wild-type and C57BL/6 mice with a targeted knockout mutation of the IL-18 gene (IL-18−/− mice). IL-18−/− mice showed much worse lung injuries than wild-type mice, as assessed by the survival rate, histological images, and leukocyte infiltration in the bronchoalveolar lavage fluid and myeloperoxidase activity. In wild-type mice, administration of IL-18 before BLM instillation resulted in suppression of lung injuries, increases in the hydroxyproline content, and decreases in the granulocyte-macrophage colony-stimulating factor content in the lung. Preadministration of IL-18 also resulted in prevention of the reduction of the lung IL-10 content caused by BLM-induced damage of alveolar epithelial. BLM instillation suppressed superoxide dismutase (SOD) activity in IL-18−/− mice to a greater extent than in wild-type mice. Pretreatment of IL-18 augmented Mn-containing superoxide dismutase (Mn-SOD) messenger RNA expression and SOD activity in the lung and prevented the reduction of SOD activity caused by BLM in both wild-type and IL-18−/− mice. These results suggest that IL-18 plays a protective role against BLM-induced lung injuries by upregulating a defensive molecule, Mn-SOD. |
| Databáze: | OpenAIRE |
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