title: 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.
authors.affiliation: Department of Bioengineering and Institute for Bioengineering and Biopharmaceutical Research, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Moonhwan
authors.initials: M
authors.lastname: Choi
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
authors.forename: Taiyoun
authors.initials: T
authors.lastname: Rhim
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002232:Carbocyanines / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism; D052638:Particulate Matter / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D055672:Static Electricity; D014162:Transfection
chemical_list: D002232:Carbocyanines; D008263:Macrophage Migration-Inhibitory Factors; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D052638:Particulate Matter; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C089187:cyanine dye 3; D003907:Dexamethasone; D011094:Polyethyleneimine
keywords: Airway inflammation; DEXA-PEI; Gene delivery; MIF; PM (particulate matter); siRNA