Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection against hyperoxic acute lung injury |
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| Institution: | 1. Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA;2. Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, South Korea;1. Department of Mathematics, University of Zagreb, Bijeni?ka 30, Zagreb, Croatia;2. Faculty of Mining, Geology and Petroleum Engineering, University of Zagreb, Pierottijeva 6, Zagreb, Croatia;1. A.I. Alikhanyan National Science Laboratory, 0036 Yerevan, Armenia;2. Departamento de Ciencias Exatas, Universidade Federal de Lavras, CP 3037, 37200-000 Lavras-MG, Brazil;3. Dipartimento di Scienza e Alta Tecnologia, Universitá degli Studi dell’Insubria, Via Valleggio 11, 22100 Como, Italy;4. I.N.F.N. Sezione di Milano, Via Celoria 16, 20133 Milano, Italy;5. Laboratoire Interdisciplinaire Carnot de Bourgogne, UMR CNRS 6303, Université de Bourgogne, 21078 Dijon Cedex, France;6. Institute for Physical Research, 0203 Ashtarak-2, Armenia;1. Servicio de Urgencias, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, España;2. Universidad Alfonso X El Sabio, Madrid, España;3. Servicio de Farmacia, Hospital Universitario Puerta de Hierro-Majadahonda, Majadahonda, Madrid, España;4. Servicio de Medicina Interna, Hospital Severo Ochoa de Leganés, Leganés, Madrid, España |
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| Abstract: | Suppressor of cytokine signaling-1 (SOCS-1) is a member of the suppressor of cytokine signaling family of proteins and an inhibitor of interleukin-6 (IL-6) signaling. SOCS-1 has been shown to protect cells from cellular damage and apoptosis induced by tumor necrosis factor (TNF), lipopolysaccharide (LPS), and interferon gamma (IL-γ). However, it is not known whether increased SOCS-1 is protective during pulmonary oxidative stress. Therefore, we hypothesized that increased SOCS-1 in the lungs of mice would be protective in the setting of hyperoxic lung injury. We administered SOCS-1 adenovirus (Ad-SOCS-1) intratracheally into the lungs and exposed the mice to 100% O2. Mice infected with GFP adenovirus (Ad-GFP) were used as controls. Mice treated with Ad-SOCS-1 had enhanced survival in 100% oxygen compared to Ad-GFP-administered mice. After 3 days of hyperoxia, Ad-GFP mice were ill and tachypnic and died after 4 days. In contrast, all Ad-SOCS-1-treated mice survived for at least 6 days in hyperoxia and 80% survived beyond 7 days. Ad-SOCS-1 transfection protected mouse lungs from injury as indicated by lower lung wet/dry weight, alveolar–capillary protein leakage, reduced infiltration of inflammatory cells, and lower content of thiobarbituric acid-reactive substances in lung homogenate. Our results also indicated that Ad-SOCS-1 significantly inhibits hyperoxia-induced ASK-1 (apoptosis signal-regulating kinase 1) expression. Taken together, these findings show that increased expression of adenovirus-mediated SOCS-1 in the lungs of mice significantly protects against hyperoxic lung injury. |
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| Keywords: | Adenovirus Acute lung injury (ALI) Suppressor of cytokine signaling-1 (SOCS-1) Hyperoxia Inflammation Apoptosis signal-regulating kinase-1 (ASK-1) |
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