Arginase I Attenuates Inflammatory Cytokine Secretion Induced by Lipopolysaccharide in Vascular Smooth Muscle Cells

• DOI: 10.1161/atvbaha.111.229302
• Publication Date: 2011-05-27T04:01:12Z
• Authors: Xu-ping Wang; Yu-guo Chen; Wei-dong Qin; Wei Zhang; Shu-jian Wei; Juan Wang; Fu Qiang Liu; Lei Gong; Feng Shuang An; Yun Zhang; Zhe-Yu Chen; Ming-Xiang Zhang
• Keywords: Lipopolysaccharides; 0303 health sciences; Arginase; Base Sequence; Myocytes, Smooth Muscle; NF-kappa B; Down-Regulation; Nitric Oxide Synthase Type II; Nitric Oxide; Monocytes; Plaque, Atherosclerotic; 3. Good health; Chemotaxis, Leukocyte; 03 medical and health sciences; Cell Movement; Animals; Cytokines; Humans; RNA Interference; Rabbits; Inflammation Mediators; RNA, Small Interfering; Cells, Cultured

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 aggravated 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.