Pigment epithelium-derived factor (PEDF) blocks angiotensin II-induced T cell proliferation by suppressing autocrine production of interleukin-2.
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 I 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.
Yamagishi
Sho-ichi
S
Department of Internal Medicine III, Kurume University School of Medicine, Japan. shoichi@med.kurume-u.ac.jp
Kikuchi
Seiji
S
Nakamura
Kazuo
K
Matsui
Takanori
T
Takeuchi
Masayoshi
M
Inoue
Hiroyoshi
H
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D017931:DNA Primers; D005136:Eye Proteins / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D019255:NADPH Oxidases / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015843:Serpins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D000804:Angiotensin II; D017931:DNA Primers; D005136:Eye Proteins; D007376:Interleukin-2; D019255:NADPH Oxidases; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D015843:Serpins; D013936:Thymidine; D000099174:Pigment Epithelium-Derived Factor