Activation and suppression of renin-angiotensin system in human dendritic cells |
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Authors: | Lapteva Natalia Ide Kazuki Nieda Mie Ando Yoshitaka Hatta-Ohashi Yoko Minami Mutsuhiko Dymshits Grigory Egawa Koichi Juji Takeo Tokunaga Katsushi |
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Institution: | Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan. |
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Abstract: | We previously identified the gene expression of renin-angiotensin system in human monocyte-derived dendritic cells (DCs). This study was conducted to examine the mechanisms by which angiotensin II and captopril, the inhibitor of the angiotensin-converting enzyme (ACE), affect human DCs. In DCs, lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-(IL)-1alpha, IL-10, IL-12, and IL-18 was significantly inhibited by captopril. In contrast, angiotensin II treatment resulted in a significant increase in TNF-alpha and IL-6 protein biosynthesis by DCs. In addition, we have studied the global expression of 2400 genes in DCs from two donors. Here, we demonstrated the specific down-regulation of the ACE gene expression in captopril-treated DCs. Our finding indicates the possible activation of NF-kappaB through the up-regulation of expressions of MEFV gene (encoding PYRIN protein) and heterogeneous nuclear ribonucleoprotein R in DCs. This is the first study on the modulation of cytokine and gene expression by angiotensin II and captopril in DCs. |
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Keywords: | Dendritic cell Renin-angiotensin Angiotensin II Captopril cDNA microarray |
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