Silencing of tumor necrosis factor receptor-1 in human lung microvascular endothelial cells using particle platforms for siRNA delivery.

Silencing of tumor necrosis factor receptor-1 in human lung microvascular endothelial cells using particle platforms for siRNA delivery. Curr Drug Targets. 2015 Jul 22; Authors: Bai L, Andersson HA, McConnell K, Chan D, Hernandez M, Gonzalez J, Liu X, La Francesca S, Sakamoto J, Serda RE Abstract Acute lung injury (ALI) and its most severe manifestation, acute respiratory distress syndrome (ARDS), is a clinical syndrome defined by acute hypoxemic respiratory failure and bilateral pulmonary infiltrates consistent with edema. In-hospital mortality is 38.5% for ALI, and 41.1% for ARDS. Activation of alveolar macrophages in the donor lung causes the release of pro-inflammatory chemokines and cytokines, such as TNF-α. To determine the relevance of TNF-α in disrupting bronchial endothelial cell function, we stimulated human THP-1 macrophages with lipopolysaccharide (LPS) and used the cytokine-supplemented media to disrupt normal endothelial cell functions. Endothelial tube formation was disrupted in the presence of LPS-activated THP-1 conditioned media, with reversal of the effect occurring in the presence of 0.1µg/ml Enbrel, indicating that TNF-α was the major serum component inhibiting endothelial tube formation. To facilitate lung conditioning, we tested liposomal and porous silicon (pSi) delivery systems for their ability to selectively silence TNFR1 using siRNA technology. Of the three types of liposomes tested, only cationic lipo...
Source: Current Drug Targets - Category: Drugs & Pharmacology Authors: Tags: Curr Drug Targets Source Type: research