RNAi-mediated suppression of constitutive pulmonary gene expression by small interfering RNA in mice

Gutbier, Birgitt; Kube, SM; Reppe, Katrin; Santel, Ansgar; Lange, Christian; Kaufmann, Jörg; Suttorp, Norbert; Witzenrath, Martin

doi:10.1016/j.pupt.2010.03.007

Cited by 49 publications

(44 citation statements)

References 30 publications

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“…These complexes were characterized by a size of almost 400 nm and a zeta potential of À8 mV. siRNA delivery has been attempted in vivo to the lung in the absence of carrying molecules and nevertheless obtaining positive results (Fulton et al, 2009;Gutbier et al, 2010;Rosas-Taraco et al, 2009;Senoo et al, 2010), with some reports showing no significant difference in gene silencing efficiency between naked siRNA and the use of delivery vectors (Bitko et al, 2005;Fulton et al, 2009). It has been hypothesized that the siRNA modifications transfection or the damage of the airway epithelium caused by viral infection, or by other pathological processes, may have caused increased internalization of naked siRNAs (Fujita et al, 2013).…”

Section: Resultsmentioning

confidence: 99%

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in airway epithelial cells

Gioia

Sardo

Belgiovine

et al. 2015

International Journal of Pharmaceutics

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Section: Resultsmentioning

confidence: 99%

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in airway epithelial cells

Gioia

Sardo

Belgiovine

et al. 2015

International Journal of Pharmaceutics

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“…MiR-155 ASOs delivery was performed 24 h after LPS administration as described previously (31). Mice were lightly anesthetized with methoxyflurane and suspended on a board in supine position at a 45-degree angle.…”

Section: Intratracheal Administration Of Mir-155 Asomentioning

confidence: 99%

Antisense Oligonucleotide Treatment Enhances the Recovery of Acute Lung Injury through IL-10–Secreting M2-like Macrophage-Induced Expansion of CD4+ Regulatory T Cells

Guo

Wen

Qin

et al. 2013

The Journal of Immunology

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MicroRNAs (miRNAs) have been shown as an important regulator in the pathologies of acute lung injury (ALI). However, the potential effect of miRNA-based therapeutic studies in ALI remains poorly understood. We assessed the effect of antisense oligonucleotides (ASOs) against miR-155 on the development of ALI using a murine ALI model. We found that miR-155 ASO treatment could enhance the recovery of ALI as evidenced by accelerated body weight back, reduced level of bronchoalveolar lavage (BAL) protein and proinflammatory cytokines, and reduced number of BAL cells. Adoptive cell transfer assay in RAG1−/− mice showed that CD4+CD25+ regulatory T cells (Tregs) mediated the enhanced recovery of ALI. Mechanistic evidence showed that enhanced expansion of Tregs in vivo, dominantly induced by IL-10–secreting M2-like macrophages, was critical for their elevated proportion in miR-155 ASO-treated ALI mice. Finally, we report that C/EBPβ, a target molecule of miR-155, was upregulated and associated with IL-10 secretion and M2-like phenotype of macrophages. These data provided a previously unknown mechanism for miRNA-based therapy against ALI, which could ultimately aid the understanding of recovery of ALI and the development of new therapeutic strategies against clinical inflammatory lung disease.

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“…16 This procedure has been used in many studies to reproducibly deposit a large volume of solution of interest in the deep lung of rodents. 21,30,31 The volume of 200 µL was chosen, because it corresponds to the maximum volume that can be administered to rats. This procedure was well tolerated and did not cause any death.…”

Section: Discussionmentioning

confidence: 99%

Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats

Hureaux

Lacoeuille

Lagarce

et al. 2017

IJN

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Lipid nanocapsules (LNCs) are potential drug carriers for pulmonary delivery since they can be nebulized without any structural or functional changes, and the aerosols produced are highly compatible with pulmonary drug delivery in human beings. The alveolar surface tension, in vitro cytotoxicity, biodistribution and pulmonary toxicity in rats of a single endotracheal spray of LNCs or paclitaxel-loaded LNCs were studied. In vitro cytotoxicity of LNCs after a spray remained unchanged. Biodistribution study showed a homogeneous repartition in the lungs in rats with an improvement in lung retention of the radiolabeled tracer loaded in LNCs compared to the absence of LNCs with a lung half-time of 8.8±0.7 hours. Bronchoalveolar fluid analysis revealed transient 7-day alveolar inflammation, reaching a maximum between days 2 and 4, characterized by a peak of granulocytes at day 1 followed by a peak of lymphocytes at day 3. Alveolar protein levels were increased at days 3 and 7. Acute inflammation was increased with paclitaxel-loaded LNCs in comparison with blank LNCs but dropped out at day 7. No histological pulmonary lesion was observed at day 60. LNCs lowered surface tension to a greater degree than Curosurf ® in a physicochemical model of the pulmonary alveolus. A single pulmonary delivery of LNCs induces a short-term alveolar inflammation with no residual lesions in rats at day 60. These data permit to start the study of LNCs in surfactant replacement therapy.

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RNAi-mediated suppression of constitutive pulmonary gene expression by small interfering RNA in mice

Cited by 49 publications

References 30 publications

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in airway epithelial cells

Cationic polyaspartamide-based nanocomplexes mediate siRNA entry and down-regulation of the pro-inflammatory mediator high mobility group box 1 in airway epithelial cells

Antisense Oligonucleotide Treatment Enhances the Recovery of Acute Lung Injury through IL-10–Secreting M2-like Macrophage-Induced Expansion of CD4+ Regulatory T Cells

Absence of lung fibrosis after a single pulmonary delivery of lipid nanocapsules in rats

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