Pigment epithelium-derived factor (PEDF) blocks angiotensin II-induced T cell proliferation by suppressing autocrine production of interleukin-2

Sho Ichi Yamagishi, Seiji Kikuchi, Kazuo Nakamura, Takanori Matsui, Masayoshi Takeuchi, Hiroyoshi Inoue

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 II-induced 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.

Original languageEnglish
Pages (from-to)265-269
Number of pages5
JournalMedicinal Chemistry
Volume2
Issue number3
DOIs
Publication statusPublished - 2006 May
Externally publishedYes

Keywords

  • Angiotensin II
  • Atherosclerosis
  • Oxidative stress
  • PEDF
  • T cells

ASJC Scopus subject areas

  • Drug Discovery

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