title: Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection against hyperoxic acute lung injury.
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.
authors: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors: Lakshmi
authors: L
authors: Galam
authors: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors: Prasanna Tamarapu
authors: PT
authors: Parthasarathy
authors: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors: Young
authors: Y
authors: Cho
authors: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors: Seong Ho
authors: SH
authors: Cho
authors: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Jeonju, South Korea.
authors: Yong Chul
authors: YC
authors: Lee
authors: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA.
authors: Richard F
authors: RF
authors: Lockey
authors: Division of Allergy and Immunology, Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA. Electronic address: nkollipu@health.usf.edu.
authors: Narasaiah
authors: N
authors: Kolliputi
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000517:prevention & control; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005260:Female; D015870:Gene Expression; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: Acute lung injury (ALI); Adenovirus; Apoptosis signal-regulating kinase-1 (ASK-1); Hyperoxia; Inflammation; Suppressor of cytokine signaling-1 (SOCS-1)