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


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.
Tone
Atsuhito
A
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan.
Shikata
Kenichi
K
Ogawa
Daisuke
D
Sasaki
Sakiko
S
Nagase
Ryo
R
Sasaki
Motofumi
M
Yozai
Kosuke
K
Usui
Hitomi Kataoka
HK
Okada
Shinichi
S
Wada
Jun
J
Shikata
Yasushi
Y
Makino
Hirofumi
H
D000804:Angiotensin II / Q000494:pharmacology*; D045744:Cell Line, Tumor; D054412:Chemokine CCL8; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D020869:Gene Expression Profiling; D006801:Humans; D007948:Leukemia, Monocytic, Acute; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
C515453:CCL8 protein, human; D054412:Chemokine CCL8; D018925:Chemokines; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II