Asymmetric dimethyl-arginine metabolism in a murine model of cigarette smoke-mediated lung inflammation

AbstractThere is increasing evidence that the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethyl-arginine (ADMA) is involved in the pathogenesis of chronic lung diseases. One important regulator of this molecule is the ADMA-metabolizing enzyme dimethyl-arginine dimethyl-aminohydrolase (DDAH). The objective of this study was to determine whether perturbation of the ADMA-DDAH pathway contributes to lung inflammation following exposure to cigarette smoke (CS). For these studies, wild-type and DDAH transgenic mice were sham or CS-exposed. Serum ADMA levels were determined by mass spectrometry. ADMA content and DDAH expression were also visualized in mouse lung tissue by immunohistochemistry. DDAH expression was determined by real-time quantitative PCR (qPCR). Inflammation was assessed by H&E staining and analyses of total cell counts and fluid tumor necrosis factor (TNF)-α levels (using ELISA) in lung lavage fluid. NF-κB binding activity in mouse lung epithelial (LA-4) cells was assessed by ...