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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Heat Stress Response and Diabetes: More Room for Mitochondrial Implication
Current Pharmaceutical Design Insulin Neuritis and Diabetic Cachectic Neuropathy: A Review
Current Diabetes Reviews Combining Bevacizumab with Radiation or Chemoradiation for Solid Tumors: A Review of the Scientific Rationale, and Clinical Trials
Current Angiogenesis (Discontinued) Adipose Tissue Oxygenation in Obesity: A Matter of Cardiovascular Risk?
Current Pharmaceutical Design Effects of Pulmonary Hypertension and Right Ventricular Function in Short and Long-Term Kidney Function
Current Cardiology Reviews Recent Advances in GNAS Epigenetic Research of Pseudohypoparathyroidism
Current Molecular Medicine Current Outcomes and Considerations in Hypoplastic Left Heart Syndrome
Current Pediatric Reviews Pregnancy, Physical Activity and Weight Control to Prevent Obesity and Future Chronic Disease Risk in Both Mother and Child
Current Women`s Health Reviews Meet the Editorial Board
Current Pharmaceutical Design Visceral Adipose Tissue and Atherosclerosis
Current Vascular Pharmacology Relationship between Hyperlipidemia, Cardiovascular Disease and Stroke: A Systematic Review
Current Cardiology Reviews Targeting Adenosine Signaling to Treatment of Diabetic Nephropathy
Current Drug Targets The Effect of Local Alcohol Delivery in Reducing Intimal Hyperplasia Induced by Vascular Injury and the Clinical Implications
Vascular Disease Prevention (Discontinued) Fine Tuning of PPAR Ligands for Type 2 Diabetes and Metabolic Syndrome
Mini-Reviews in Medicinal Chemistry Clinical Pharmacotherapy for Obesity: Current Drugs and Those in Advanced Development
Current Drug Targets Pharmacovigilance and the Cardiovascular System: Two Sides to Every Story
Current Drug Safety Computer Aided Systems for Diabetic Retinopathy Detection Using Digital Fundus Images: A Survey
Current Medical Imaging Therapeutic Implications of Immune-endocrine Interactions in the Critically Ill Patients
Current Drug Targets - Immune, Endocrine & Metabolic Disorders A Review of Patents on Therapeutic Potential and Delivery of Hydroge n Sulfide
Recent Patents on Drug Delivery & Formulation Efficacy and Safety Profile of Aliskiren: Practical Implications for Clinicians
Current Drug Safety