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
Medicinal Chemistry
Title: Pigment Epithelium-Derived Factor (PEDF) Blocks Angiotensin IIInduced T Cell Proliferation by Suppressing Autocrine Production of Interleukin-2
Volume: 2 Issue: 3
Author(s): Hiroyoshi Inoue, Masayoshi Takeuchi, Takanori Matsui, Sho-ichi Yamagishi, Seiji Kikuchi and Kazuo Nakamura
Affiliation:
Keywords: T cells, PEDF, oxidative stress, angiotensin II, Atherosclerosis
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.
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Cite this article as:
Inoue Hiroyoshi, Takeuchi Masayoshi, Matsui Takanori, Yamagishi Sho-ichi, Kikuchi Seiji and Nakamura Kazuo, Pigment Epithelium-Derived Factor (PEDF) Blocks Angiotensin IIInduced T Cell Proliferation by Suppressing Autocrine Production of Interleukin-2, Medicinal Chemistry 2006; 2 (3) . https://dx.doi.org/10.2174/157340606776930826
DOI https://dx.doi.org/10.2174/157340606776930826 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
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