ABSTRACT
Vaccinia virus infection was diagnosed in five male workers directly exposed to rabbit-skin powder contaminated by vaccinia virus via skin contact and inhalation. Four of the workers had been vaccinated against smallpox. Their clinical symptoms were severe, especially in the lungs; however, all symptoms improved after treatment.
Subject(s)
Occupational Exposure/adverse effects , Respiratory Tract Infections/etiology , Vaccinia/etiology , Animals , Humans , Male , Powders , RabbitsABSTRACT
Considerable attentions have been focused on the treatment of lung injury using mesenchymal stem cells that can replenish damaged tissues including the blood vessels. In human lung-derived mesenchymal stem cells (hL-MSC), we investigated the potential role of an IL-1ß-stimulated miR-433 pathway in angiogenesis in vitro. The expressions of miR-433 and its target genes were examined in cells treated with IL-1ß. The angiogenic activity of hL-MSC was studied by cell migration and tube formation assays in which miR-433 levels were manipulated. The reporter assay and chromatin immunoprecipitation (ChIP) were also performed to analyze the underlying regulations. We found that the expression of miR-433 was enhanced in hL-MSC by IL-1ß in a NF-κB dependent manner via a NF-κB binding site at its promoter region. The effects of IL-1ß on promoting angiogenic activities in hL-MSC can be mimicked by the overexpression of miR-433 and were blocked by anti-miR-433. Mechanistically, our data suggested that miR-433 directly targets the 3'-UTR of Dickkopf Wnt signaling pathway inhibitor 1 (DKK1) mRNA and decreases its expression. Consistently, the expression of ß-catenin, the major mediator of canonical Wnt pathway that is capable of inducing endothelial differentiation and angiogenesis, was upregulated by IL-1ß through miR-433. Thus, increasing miR-433 expression by IL-1ß in mesenchymal stem cells could stimulate their capacity of vascular remodeling for efficient repair processes, which may be utilized as a therapeutic target in patients suffering from severe lung injury.