Silver nanoparticles modify VEGF signaling pathway and mucus hypersecretion in allergic airway inflammation

Sunhyae Jang^1,*, Ji Won Park^2,*, Hye Rim Cha¹, Sun Young Jung¹, Jeong Eun Lee¹, Sung Soo Jung¹, Ju Ock Kim¹, Sun Young Kim¹, Choong Sik Lee³, Hee Sun Park<sup>1

1</sup>Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Chungnam National University Medical School, Daejeon, ²Division of Pulmonology, Department of Internal Medicine, Daejeon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, ³Department of Pathology, Chungnam National University Medical School, Daejeon, South Korea

*These authors contributed equally to this work

Abstract: The anti-inflammatory action of silver nanoparticles (NPs) has been reported in a murine model of asthma in a previous study. But more specific mechanisms of silver NPs in an attenuation of allergic airway inflammation have not yet been established. Vascular and mucous changes are believed to contribute largely in pathophysiology in asthma. Among various factors related to vascular changes, vascular endothelial growth factor (VEGF) plays a pivotal role in vascular changes in asthma. Mucin proteins MUC5AC and MUC5B have been implicated as markers of goblet cell metaplasia in lung pathologies. The aim of this study was to investigate the effects of silver NPs on VEGF signaling pathways and mucus hypersecretion. Ovalbumin (OVA)-inhaled female BALBc mice were used to evaluate the role of silver NPs and the related molecular mechanisms in allergic airway disease. In this study, with an OVA-induced murine model of allergic airway disease, it was found that the increased levels of hypoxia-inducible factor (HIF)-1α, VEGF, phosphatidylinositol-3 kinase (PI3K) and phosphorylated-Akt levels, and mucous glycoprotein expression (Muc5ac) in lung tissues were substantially decreased by the administration of silver NPs. In summary, silver NPs substantially suppressed mucus hypersecretion and PI3K/HIF-1α/VEGF signaling pathway in an allergic airway inflammation.

Keywords: allergic airway disease, hypoxia inducible factor-1α, vascular endothelial growth factor