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

Atsuhito Tone, Kenichi Shikata, Daisuke Ogawa, Sakiko Sasaki, Ryo Nagase, Motofumi Sasaki, Kosuke Yozai, Hitomi Kataoka, Shinichi Okada, Jun Wada, Yasushi Shikata, Hirofumi Makino

Research output: Contribution to journalArticle

19 Citations (Scopus)

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 (CV 11974). 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 (CV 11974) 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.

Original languageEnglish
Pages (from-to)45-50
Number of pages6
JournalJRAAS - Journal of the Renin-Angiotensin-Aldosterone System
Volume8
Issue number1
DOIs
Publication statusPublished - Mar 2007

Fingerprint

Chemokine CCL8
Transcriptome
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Macrophages
Diabetic Nephropathies
Oligonucleotide Array Sequence Analysis
Real-Time Polymerase Chain Reaction
Atherosclerosis
Monocytes
Leukemia
Anti-Inflammatory Agents
Up-Regulation

Keywords

  • Angiotensin II
  • Candesartan
  • Chemokine
  • DNA array
  • Macrophage
  • MCP-2
  • Renin-Angiotensin system
  • THP-1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Changes of gene expression profiles in macrophages stimulated by angiotensin II - Angiotensin II induces MCP-2 through AT1-receptor. / Tone, Atsuhito; Shikata, Kenichi; Ogawa, Daisuke; Sasaki, Sakiko; Nagase, Ryo; Sasaki, Motofumi; Yozai, Kosuke; Kataoka, Hitomi; Okada, Shinichi; Wada, Jun; Shikata, Yasushi; Makino, Hirofumi.

In: JRAAS - Journal of the Renin-Angiotensin-Aldosterone System, Vol. 8, No. 1, 03.2007, p. 45-50.

Research output: Contribution to journalArticle

Tone, Atsuhito ; Shikata, Kenichi ; Ogawa, Daisuke ; Sasaki, Sakiko ; Nagase, Ryo ; Sasaki, Motofumi ; Yozai, Kosuke ; Kataoka, Hitomi ; Okada, Shinichi ; Wada, Jun ; Shikata, Yasushi ; Makino, Hirofumi. / Changes of gene expression profiles in macrophages stimulated by angiotensin II - Angiotensin II induces MCP-2 through AT1-receptor. In: JRAAS - Journal of the Renin-Angiotensin-Aldosterone System. 2007 ; Vol. 8, No. 1. pp. 45-50.
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T1 - Changes of gene expression profiles in macrophages stimulated by angiotensin II - Angiotensin II induces MCP-2 through AT1-receptor

AU - Tone, Atsuhito

AU - Shikata, Kenichi

AU - Ogawa, Daisuke

AU - Sasaki, Sakiko

AU - Nagase, Ryo

AU - Sasaki, Motofumi

AU - Yozai, Kosuke

AU - Kataoka, Hitomi

AU - Okada, Shinichi

AU - Wada, Jun

AU - Shikata, Yasushi

AU - Makino, Hirofumi

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N2 - 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 (CV 11974). 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 (CV 11974) 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.

AB - 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 (CV 11974). 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 (CV 11974) 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.

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KW - Candesartan

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KW - Renin-Angiotensin system

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