Dexamethasone-conjugated polyethylenimine/MIF siRNA complex regulation of particulate matter-induced airway inflammation

Abstract

Inhalation of airborne particulate matter (PM), such as silicon dioxide (SiO2) and titanium dioxide (TiO2), induces acute lung inflammation. siRNA therapy has been proposed as a method to repair acute lung inflammation. To determine whether DEXA-PEI/MIF siRNA contributes to SiO2-induced acute lung inflammation repair, we administered Dexa-PEI/MIF siRNA in SiO2-treated Beas-2b cells and instilled DEXA-PEI-MIF siRNA intratracheally in mice with SiO2-induced acute lung inflammation. Using genetic (MIF mRNA RT-PCR), histological (H&E and PAS) and immunohistochemical (MIF and Muc5ac) analyses, we estimated the acute lung inflammation in Beas-2b cells and BALB/c mice. Cells and mice treated with SiO2 particles demonstrated pulmonary inflammation. DEXA-PEI/MIF siRNA restricted the extent of the pulmonary inflammation reaction to SiO2 in cells and mice. In case of SiO2-treated Beas-2b cells, only DEXA-PEI treatment failed to effectively regulate MIF mRNA release. At the same time, only DEXA-PEI treatment adjusted the amount of MIF mRNA to some extent in SiO2-treated BALB/c mice. siRNA treatment did not markedly control MIF mRNA release in mice. We also observed that the amount of MIF mRNA was decreased in cells and mice treated with DEXA-PEI/MIF siRNA. The increase of MIF mRNA markedly increased Muc5ac; in contrast, the decrease of MIF mRNA using DEXA-PEI/MIF siRNA effectively lowered Muc5ac in SiO2-treated cells and mice. These results suggest that DEXA-PEI plays a role in delivering siRNA to the nucleus as a carrier and limits the extent of acute lung inflammation. MIF siRNA also contributed to the reparative lung response in SiO2-induced pulmonary inflammation. (C) 2013 Elsevier Ltd. All rights reserved.