Authors: Yamagishi, Sho-ichi; Kikuchi, Seiji; Nakamura, Kazuo; Matsui, Takanori; Takeuchi, Masayoshi; Inoue, Hiroyoshi

Source: Medicinal Chemistry, Volume 2, Number 3, May 2006 , pp. 265-269(5)

Publisher: Bentham Science Publishers

Abstract:

Angiotensin II (Ang II) elicits numerous inflammatory-proliferative responses in vascular cells, thereby being involved in atherosclerosis. We have previously shown that pigment epithelium-derived factor (PEDF) blocks the Ang IIinduced endothelial cell activation, thus suggesting that PEDF may play a role in atherosclerosis. However, effects of PEDF on T cell activation, another key steps of atherosclerosis, remain to be elucidated. In this study, we examined whether PEDF could inhibit the Ang II-induced MOLT-3 T cell proliferation in vitro and the way that it might achieve this effect. Ang II significantly stimulated DNA synthesis in MOLT-3 T cells, which was inhibited by PEDF, olmesartan, an Ang II type 1 receptor blocker, an anti-oxidant N-acetylcysteine (NAC), or antibodies directed against IL-2. PEDF or NAC suppressed gene expression of interleukin-2 (IL-2) in Ang II-exposed MOLT-3 T cells. Furthermore, PEDF blocked the Ang II-induced reactive oxygen species (ROS) generation and NADPH oxidase activity in MOLT-3 T cells. These results demonstrate that PEDF inhibits the Ang II-induced T cell proliferation by blocking autocrine production of IL-2 via suppression of NADPH oxidase-mediated ROS generation. Blockade by PEDF of T cell activation may become a novel therapeutic target for atherosclerosis.

Keywords: Atherosclerosis; angiotensin II; oxidative stress; PEDF; T cells

Document Type: Research article

DOI: http://dx.doi.org/10.2174/157340606776930826

Affiliations: 1: Department of Internal Medicine III, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.

Publication date: 2006-05-01

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• In this Subject: Chemistry ,  Medicine (General) ,  Pharmacology
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