Adenovirus-mediated overexpression of soluble ST2 provides a protective effect on lipopolysaccharide-induced acute lung injury in mice.

摘要: Acute lung injury is characterized by a diffuse inflammatory parenchymal process, implicated in the context of significant morbidity and mortality. Previously, we have reported that soluble ST2 (sST2), member Toll-interleukin (IL)-1 receptor (TIR) superfamily, represses proinflammatory cytokine production macrophage exposed to lipopolysaccharide (LPS). In this study, examined possibility modulating LPS-induced murine pulmonary damage recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration Ad-sST2-Fc led profound decrease bronchoalveolar lavage leucocyte exudation tissue myeloperoxidase activity (reflecting phagocyte infiltration). Histological examination revealed alveolitis with cell infiltration alveolar haemorrhage airspace was less severe Ad-sST2-Fc-treated mice when compared control groups. addition, high levels vivo reduced transcription tumour necrosis factor-α, IL-6 Toll-like receptor-4 remarkably, suppressed nuclear translocation factor-κB tissues response LPS challenge. Taken together, these results suggested transfer may therapeutic potential for immunomodulatory treatment LPS-mediated injury.