Adenovirus-mediated transfer of the SOCS-1 gene to mouse lung confers protection against hyperoxic acute lung injury

作者：Galam Lakshmi; Parthasarathy Prasanna Tamarapu; Cho Young; Cho Seong Ho; Lee Yong Chul; Lockey Richard F; Kolliputi Narasaiah^*

来源：Free Radical Biology and Medicine, 2015, 84: 196-205.

DOI：10.1016/j.freeradbiomed.2015.03.036

• Adenovirus
• Acute lung injury (ALI)
• Suppressor of cytokine signaling (SOCS-1)
• Hyperoxia
• Inflammation
• Apoptosis signal-regulating kinase-1 (ASK-1)

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-gamma). 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%. O-2. Mice infected With GFP adenovirus (AcKFP) 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.

• 出版日期2015-7