Lentivirus-mediated overexpression of suppressor of cytokine signaling-3 reduces neutrophilic airway inflammation by suppressing T-helper 17 responses in mice with chronic Pseudomonas�aeruginosa lung infections
International Journal of Molecular Medicine
The aim of the present study was to explore the effect of overexpressed suppressor of cytokine signaling-3 (SOcS3) on T-helper (Th)17 cell responses and neutrophilic airway inflammation in mice with chronic Pseudomonas aeruginosa (PA) infections. SOcS3 expression was enhanced via the administration of tail vein injections of therapeutic lentivirus in mice with chronic PA lung infections. SOcS3 expression in the blood and lung tissue was assessed using reverse transcription-quantitative
... antitative polymerase chain reaction (RT-qPcR) and western blot analysis. Total and differential cell numbers and myeloperoxidase levels in the bronchoalveolar lavage (BAL) fluid were assessed, as well as the number of bacterial colonies in the lungs. Histological analysis of lung tissue was performed using hematoxylin and eosin staining and phosphorylated-signal transducer and activator of transcription-3 (p-STAT3) expression was measured by western blot analysis and immunohistochemistry. The expression of STAT3 mRNA and retinoid-related orphan receptor (ROR)γt were measured by RT-qPcR. The percentage of interleukin (IL)-17 + cells among cluster of differentiation (cd)4 + cells was calculated using flow cytometry and levels of IL-17A and IL-6 were assessed by ELISA. The expression of SOCS3 was significantly increased in cd4 + T cells following lentivirus injection and the inflammation of neutrophilic airways was notably ameliorated. Enhanced SOcS3 expression was associated with a significant decrease in the expression of p-STAT3 and RORγt in cd4 + T cells. Additionally, the percentage of IL-17 + cells among cd4 + T cells and the IL-17 contents in the BAL fluid were significantly decreased. Lentivirus-mediated overexpression of SOcS3 was revealed to ameliorate neutrophilic airway inflammation by inhibiting pulmonary Th17 responses in mice with chronic PA lung infections.