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Pigment Epithelium-Derived Factor (PEDF) Blocks Angiotensin IIInduced T Cell Proliferation by Suppressing Autocrine Production of Interleukin-2

[ Vol. 2 , Issue. 3 ]

Author(s):

Hiroyoshi Inoue, Masayoshi Takeuchi, Takanori Matsui, Sho-ichi Yamagishi, Seiji Kikuchi and Kazuo Nakamura   Pages 265 - 269 ( 5 )

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:

T cells, PEDF, oxidative stress, angiotensin II, Atherosclerosis

Affiliation:

Department of InternalMedicine III, Kurume University School of Medicine, 67 Asahi-machi,Kurume 830-0011, Japan.



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