Arginase I Attenuates Inflammatory Cytokine Secretion Induced by Lipopolysaccharide in Vascular Smooth Muscle Cells
Objective—Inflammation plays an important role in atherosclerosis. Arginase I (Arg I) promotes the proliferation of vascular smooth muscle cells; however, the effect of Arg I on inflammation remains unknown. The present study investigated the role of Arg I in inflammation in vitro and in vivo.
Methods and Results—Quantitative reverse transcription–polymerase chain reaction and Western blot analysis demonstrated that Arg I inhibited tumor necrosis factor-α production induced by lipopolysaccharide in human aortic smooth muscle cells. Inducible nitric oxide synthase substrate competition and nuclear factor-κB activation were main contributors to lipopolysaccharide-mediated inflammatory cytokine generation. However, Arg I could attenuate the function of inducible nitric oxide synthase and inhibit the subsequent nuclear factor-κB activation, leading to inhibition of tumor necrosis factor-α generation. Furthermore, upregulation of Arg I significantly decreased macrophage infiltration and inflammation in atherosclerotic plaque of rabbits, whereas downregulation of Arg I aggregated these adverse effects.
Conclusion—The results indicate the antiinflammatory effects of Arg I and suggest an unexpected beneficial role of Arg I in inflammatory disease.
- Received November 21, 2010.
- Accepted May 12, 2011.
- © 2011 American Heart Association, Inc.