title: Activation and suppression of renin-angiotensin system in human dendritic cells.
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.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lapteva
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ide
authors.forename: Mie
authors.initials: M
authors.lastname: Nieda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ando
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hatta-Ohashi
authors.forename: Mutsuhiko
authors.initials: M
authors.lastname: Minami
authors.forename: Grigory
authors.initials: G
authors.lastname: Dymshits
authors.forename: Koichi
authors.initials: K
authors.lastname: Egawa
authors.forename: Takeo
authors.initials: T
authors.lastname: Juji
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
mesh_terms: 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
chemical_list: D016207:Cytokines; D017931:DNA Primers; D018836:Inflammation Mediators; D000804:Angiotensin II; D002216:Captopril