Activation and suppression of renin-angiotensin system in human dendritic cells.
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.
Lapteva
Natalia
N
Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
Ide
Kazuki
K
Nieda
Mie
M
Ando
Yoshitaka
Y
Hatta-Ohashi
Yoko
Y
Minami
Mutsuhiko
M
Dymshits
Grigory
G
Egawa
Koichi
K
Juji
Takeo
T
Tokunaga
Katsushi
K
D000804:Angiotensin II / Q000494:pharmacology; D001483:Base Sequence; D002216:Captopril / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D000804:Angiotensin II; D002216:Captopril