title: Adenovirus-mediated overexpression of soluble ST2 provides a protective effect on lipopolysaccharide-induced acute lung injury in mice.
abstract: 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), a member of the Toll-interleukin (IL)-1 receptor (TIR) superfamily, represses proinflammatory cytokine production of macrophage exposed to lipopolysaccharide (LPS). In this study, we examined the possibility of modulating LPS-induced murine inflammatory pulmonary damage by recombinant adenovirus-mediated sST2-Fc (Ad-sST2-Fc) gene transfer. Single intranasal administration of Ad-sST2-Fc led to a profound decrease in LPS-induced bronchoalveolar lavage leucocyte exudation and lung tissue myeloperoxidase activity (reflecting phagocyte infiltration). Histological examination revealed alveolitis with inflammatory cell infiltration and alveolar haemorrhage in the alveolar airspace was less severe in Ad-sST2-Fc-treated mice when compared with control groups. In addition, high levels of sST2-Fc in vivo reduced the transcription of tumour necrosis factor-α, IL-6 and Toll-like receptor-4 gene remarkably, and suppressed the nuclear translocation of nuclear factor-κB in lung tissues in response to LPS challenge. Taken together, these results suggested that administration of Ad-sST2-Fc gene transfer may have therapeutic potential for the immunomodulatory treatment of LPS-mediated inflammatory lung injury.
authors.affiliation: Department of Microbiology and Immunology, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Yin
authors.forename: X Y
authors.initials: XY
authors.lastname: Li
authors.forename: B H
authors.initials: BH
authors.lastname: Yuan
authors.forename: B B
authors.initials: BB
authors.lastname: Zhang
authors.forename: S L
authors.initials: SL
authors.lastname: Hu
authors.forename: H B
authors.initials: HB
authors.lastname: Gu
authors.forename: X B
authors.initials: XB
authors.lastname: Jin
authors.forename: J Y
authors.initials: JY
authors.lastname: Zhu
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use*; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control; D007155:Immunologic Factors / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007962:Leukocytes / Q000276:immunology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology / Q000627:therapeutic use; D012995:Solubility; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000235:genetics; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; C486189:Il1rl1 protein, mouse; D007155:Immunologic Factors; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4