Changes of gene expression profiles in macrophages stimulated by angiotensin II--angiotensin II induces MCP-2 through AT1-receptor.

Abstract

INTRODUCTION:

Macrophages play critical roles in the development of atherosclerosis and diabetic nephropathy as well as many inflammatory diseases. Angiotensin II type 1 receptor antagonists (AIIA) are beneficial for the prevention of atherosclerosis and diabetic nephropathy suggesting that angiotensin II (Ang II) promotes the development of these diseases. It has recently been reported that Ang II exerts proinflammatory actions in vivo and in vitro. This study was aimed to clarify the direct effects of Ang II on monocytes/macrophages.

MATERIALS AND METHODS:

PMA-treated THP-1 cells, a human monocytic leukaemia cell line, were treated with Ang II (10-6 mol/L) for 24 hours with or without AIIA (CV11974). We evaluated gene expression profiles of these cells using DNA microarray system and quantified them by real-time RT-PCR.

RESULTS:

DNA microarray revealed that in total 19 genes, including monocyte chemoattractant protein (MCP)-2, were up-regulated by Ang II and down-regulated by AIIA. Real-time RT-PCR showed that up-regulation of MCP-2 with Ang II is blocked by the AIIA (CV11974) but not by an AT2-receptor antagonist.

CONCLUSIONS:

These results suggest that Ang II directly stimulates MCP-2 expression through AT1-receptors in activated macrophages. Ang II may contribute to the persistence or amplification of microinflammation in vessel walls, heart and kidney. Vasculoprotective or renoprotective effects of AIIA might partly depend on direct anti-inflammatory effects on macrophages.

• Authors: Atsuhito Tone, Kenichi Shikata, Daisuke Ogawa, Sakiko Sasaki, Ryo Nagase, Motofumi Sasaki, Kosuke Yozai, Hitomi Kataoka Usui, Shinichi Okada, Jun Wada, Yasushi Shikata, Hirofumi Makino
• Journal: Journal of the renin-angiotensin-aldosterone system : JRAAS (J Renin Angiotensin Aldosterone Syst) Vol. 8 Issue 1 Pg. 45-50 (Mar 2007) ISSN: 1470-3203 [Print] England
• PMID: 17487826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CCL8 protein, human
• Chemokine CCL8
• Chemokines
• Cytokines
• Monocyte Chemoattractant Proteins
• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Vasoconstrictor Agents
• Angiotensin II

Topics

• Angiotensin II (pharmacology)
• Cell Line, Tumor
• Chemokine CCL8
• Chemokines (genetics)
• Cytokines (genetics)
• Gene Expression (drug effects, immunology)
• Gene Expression Profiling
• Humans
• Leukemia, Monocytic, Acute
• Macrophages (cytology, drug effects, physiology)
• Monocyte Chemoattractant Proteins (genetics)
• Monocytes (cytology, drug effects, physiology)
• Oligonucleotide Array Sequence Analysis
• Receptor, Angiotensin, Type 1 (genetics)
• Receptor, Angiotensin, Type 2 (genetics)
• Vasoconstrictor Agents (pharmacology)