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Oxidative Medicine and Cellular Longevity
Volume 2014 (2014), Article ID 148798, 10 pages
http://dx.doi.org/10.1155/2014/148798
Research Article

Atorvastatin Represses the Angiotensin 2-Induced Oxidative Stress and Inflammatory Response in Dendritic Cells via the PI3K/Akt/Nrf 2 Pathway

1Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai 200032, China
2Institute of Biomedical Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China

Received 12 March 2014; Revised 11 June 2014; Accepted 11 June 2014; Published 3 July 2014

Academic Editor: Ryuichi Morishita

Copyright © 2014 Yuanji Ma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play a complex role in both the initiation and progression of atherosclerosis. We tested the hypothesis that the anti-inflammatory and antioxidant effects of atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein kinase B/transcription factor nuclear factor-erythroid 2-related factor 2 (PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the inflammatory and oxidative stress responses. This study showed that angiotensin 2 (Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86 expression, and increased the secretion of IL-12p70, IL-6, and TNF-α. These effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2 via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a process that was reversed by the PI3K inhibitor LY294002. Therefore, the regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in the regulation of the statin-mediated antioxidant and anti-inflammatory responses in DCs.