MIF siRNA를 이용한 미세 먼지에 의한 폐기관지 염증 조절

Abstract

Inhalation of the airborne particulate matters (PM) such as SiO2 and TiO2 induce the acute lung inflammation. The strategy of siRNA therapy has been proposed as a method of repair of acute lung inflammation. But, many studies have produced arguable results. We hypothesized that DEXA-PEI-conjugated MIF siRNA (DEXA-PEI-MIF siRNA) regulates the amount of MIF mRNA release and plays a role of a down-regulating lung response in SiO2-induced acute lung inflammation. To determine whether DEXA-PEI-MIF siRNA contributes SiO2-induced acute lung inflammation repair, we treated DEXA-PEI-MIF siRNA in SiO2-treated Beas-2b cell and instilled DEXA-PEI-MIF siRNA through intratrachea of mice in the SiO2-induced acute lung inflammation. Using genetic (MIF mRNA reverse transcription PCR), histology (H&E and PAS stain),immunohistochemistry (MIF and Muc5ac) analysis, we estimated the acute lung inflammation in Beas-2b cells and Balb/c mice. Cells and mice treated with SiO2 particles were induced pulmonary inflammation. DEXA-PEI-MIF siRNA restricted the extent of lung pulmonary inflammation reaction to SiO2 in cells and mice. In case of SiO2-treated Beas-2b cell, only DEXA-PEI treatment didn’t regulate MIF mRNA release effectively. However, only DEXA-PEI treatment adjusted the amount of MIF mRNA to some extent in SiO2-treated BALB/c mice. The only MIF siRNA treatment didn’t control MIF mRNA release markedly in mice. And we 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, contrariwise, the decrease of MIF mRNA by using DEXA-PEI-MIF siRNA effectively decreased Muc5ac in SiO2-treated cells and mice. These results suggest that DEXA-PEI plays a role of delivering siRNA to nucleus as carrier and limits the extend of acute lung inflammation. MIF siRNA also contributes repairing lung response in SiO2-induced pulmonary inflammation.