Anti-Inflammatory Therapeutic Effect of Adiponectin Gene Delivery Using a Polymeric Carrier in an Acute Lung Injury Model

초록

Purpose Adiponectin (APN) is an adipokine with antiinflammatory and cytoprotective effects. In this study, the therapeutic effect of APN gene delivery using a polymeric carrier was evaluated in an acute lung injury (ALI) model. Methods Polyethylenimine (2 kDa, PEI2K), PEI25K (25 kDa), polyamidoamine (generation 2, PAMG2), dexamethasone-conjugated PEI2k (PEI2K-Dexa), and dexamethasone-conjugated PAMG2 (PAMG2-Dexa) were evaluated in vitro and in vivo as gene carriers. Formation of plasmid DNA (pDNA)/carrier complexes was confirmed by gel retardation and heparin competition assays. Delivery efficiency was measured by a luciferase assay and fluorescence microscopy. In an ALI animal model, pAPN/carrier complexes were delivered by intratracheal administration. Therapeutic effects were evaluated by cytokine assays and hematoxylin and eosin (H&E) staining. Results Gel retardation assays showed that PEI2K-Dexa and PAMG2-Dexa formed complexes with pDNA. In L2 lung epithelial cells, PAMG2-Dexa yielded higher transfection efficiency than PEI2K, PAMG2, PEI25K, lipofectamine, and PEI2K-Dexa. In vivo experiments showed that PAMG2-Dexa delivered DNA more efficiently to lung tissue than PEI2KDexa and PEI25K. Delivery of pAPN/PAMG2-Dexa complexes upregulated APN expression in the lungs of mice with ALI. As a result, the levels of pro-inflammatory cytokines such as TNF-alpha and IL-1 beta were decreased. H&E staining showed that inflammation in the lungs of mice with ALI was reduced by delivery of the APN gene. Conclusion Delivery of the APN gene using PAMG2-Dexa reduced inflammation in the lungs of mice with ALI. The APN gene could be a useful tool in the development of gene therapy for ALI.

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