ABSTRACT
Recent studies suggest that cigarette smoking may trigger the development of psoriasis through oxidative, inflammatory and genetic mechanisms. Smoking initiates formation of free radicals that stimulate cell signalling pathways active in psoriasis including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT). Smoking damages the skin by increasing formation of reactive oxygen species and decreasing the gene expression of antioxidants. Nicotine also stimulates innate immune cells integral to the pathogenesis of psoriasis including dendritic cells, macrophages and keratinocytes. These cells release cytokines that activate T lymphocytes and perpetuate a cycle of chronic inflammation. Smoking also enhances expression of genes known to confer an increased risk of psoriasis, including HLA-Cw6, HLA-DQA1*0201 and CYP1A1. Improved understanding of the possible link between smoking and psoriasis pathogenesis may provide further insight into mechanisms underlying smoking, psoriasis and risk of subsequent cardiovascular disease.
Subject(s)
Psoriasis/etiology , Smoking/adverse effects , Animals , Antioxidants/metabolism , Gene Expression Regulation/genetics , Humans , Immune Tolerance , Immunity, Cellular , Mice , Microvessels/physiology , Neovascularization, Pathologic/etiology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Oxidants/metabolism , Psoriasis/immunology , Reactive Nitrogen Species/metabolism , Skin/blood supply , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Theophylline is a potent bronchodilator with a narrow therapeutic index. A simple fluorescent biosensor that detects clinically relevant theophylline concentrations has been developed using the well-characterized theophylline binding RNA aptamer. Hybridization of the RNA aptamer to a fluorescently labeled DNA strand (FL-DNA) yields a fluorescent RNA:DNA hybrid that is sensitive to theophylline. The biosensor retains the remarkable selectivity of the RNA aptamer for theophylline over caffeine and is sensitive to 0-2 muM theophylline, well below the clinically relevant concentration (5-20 mg/L or approximately 10-50 muM). Adding a dabcyl quenching dye to the 3'-terminus of the fluorescently labeled DNA strand yielded a dual-labeled DNA strand (FL-DNA-Q) and increased the dynamic range of this simple biosensor from 1.5-fold to 4-fold.
