학술논문

Preventive Effect of Pentoxifylline on Cyclosporine A-Induced Collagen Synthesis in Calf Pulmonary Artery Endothelial Cells
Document Type
Academic Journal
Source
Annals of Surgical Treatment and Research. 2009-03 76(3):135-143
Subject
Cyclosporine A
Pentoxifylline
Collagen type Ⅰ
Cyclic GMP
Nitric oxide
Language
Korean
ISSN
2288-6575
2288-6796
Abstract
Purpose: Cyclosporine A (CsA) is a potent immunosuppressive agent, and it has been used to prevent rejection of transplanted organs and to treat autoimmune diseases. Many side effects of CsA, including various types of endothelial dysfunction, have been reported. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor that is used for the treatment of peripheral vascular diseases. Methods: We investigated the effect of CsA on collagen synthesis and clarified whether PTX has protective effects against CsA-induced arterial vasculopathy using calf pulmonary artery endothelial cells. This study was carried out using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), Western blot analysis, nitric oxide (NO) detection, and cyclic guanosine monophosphate (cGMP) enzyme immunoassay. Results: CsA treatment significantly increased the expression of collagen type I mRNA and protein and decreased the production of NO and cGMP. However, pre-treatment with PTX exerted anticollagen effect by suppressing the CsA-induced formation of collagen, but this effect of PTX was not modulated by NO and cGMP. Conclusion: Based on the present results, it is expected that PTX may have a protective effect against CsA-induced arterial vasculopathy, although the mechanism of PTX needs to be clarified in future studies.