carbocyanines and Idiopathic-Pulmonary-Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating and fatal interstitial lung disease due to various challenges in diagnosis and treatment. Due to its complicated pathogenesis and difficulty in early diagnosis, there is no effective cure. Cyclooxygenase-2 (COX-2) is inextricably associated with pulmonary fibrosis. The abnormal level of COX-2 leads to extremely exacerbated pulmonary fibrosis. Therefore, we reported a near-infrared fluorescent probe Cy-COX to detect the fluctuation of COX-2 levels during pulmonary fibrosis and explain its important protective effect. The probe Cy-COX showed a significant enhancement of fluorescence signal to COX-2 with excellent selectivity and sensitivity. In order to clarify the relationship between COX-2 and pulmonary fibrosis, we used the probe Cy-COX to detect COX-2 fluctuation in organisms with pulmonary fibrosis. The results showed that the COX-2 level increased in the early stage and decreased in the late stage with the aggravation of pulmonary fibrosis. Furthermore, up-regulation of COX-2 levels can effectively alleviate the severity of pulmonary fibrosis. Therefore, Cy-COX is a fast and convenient imaging tool with great potential to predict the early stage of pulmonary fibrosis and evaluate the therapeutic effects.

Topics: Animals; Carbocyanines; Cells, Cultured; Cyclooxygenase 2; Disease Models, Animal; Fluorescent Dyes; Idiopathic Pulmonary Fibrosis; Infrared Rays; Mice; Mice, Inbred C57BL; Optical Imaging; Rats

Idiopathic pulmonary fibrosis (IPF) is a lung-limited and progressive fibrotic disease. The early diagnosis and therapies of IPF are still full of clinical challenges. Glutathione S-transferase (GSTs) plays significant roles in promoting the formation of pulmonary fibrosis. Herein, we report a fluorescent probe (Cy-GST) for the detection of GSTs concentration fluctuations in cells and in mice models. The probe can selectively and sensitively respond to GSTs with an "off-on" type fluorescence switch. Our results demonstrated that the level of intracellular GSTs increase in the pulmonary fibrosis cells and mice models. And the IPF patients hold high levels of GSTs concentrations. Thus, GSTs are likely to play important roles in pulmonary fibrosis. The inhibitor of GSTs TLK117 can reduce the severity of pulmonary fibrosis. The synergistic treatment of TLK117 and pirfenidone have better therapeutic effects than only using pirfenidone in pulmonary fibrosis mice models. The level of GSTs in IPF may be a new potential marker for IPF diagnosis. And the inhibition of GSTs may be a new therapeutic strategy for IPF treatment.

Topics: Animals; Carbocyanines; Disease Models, Animal; Enzyme Inhibitors; Fluorescent Dyes; Glutathione; Glutathione Transferase; Idiopathic Pulmonary Fibrosis; Infrared Rays; Mice; Mice, Inbred C57BL; Optical Imaging; Particle Size; Surface Properties