Down-regulation by a new anti-inflammatory compound, FR167653, of differentiation and maturation of human monocytes and bone marrow CD34+ cells to dendritic cells.
FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate), one of the pyridinyl imidazoles, is an immunosuppressive agent which was developed to inhibit proinflammatory cytokine production. We examined the effect of FR167653 on the differentiation and maturation phases of both human bone marrow-derived dendritic cells (BM-DC) and blood monocyte-derived DC (Mo-DC). DC induced from either BM-DC or Mo-DC progenitors in the presence of FR167653 had lower expression of CD1a, CD83 and CD86 (B7.2). FR167653 also significantly suppressed the ability of Mo-DC to produce both TNF-alpha and IL-1beta in response to LPS stimulation. Mixed lymphocyte reaction (MLR) stimulation was significantly lower in FR167653-treated Mo-DC than in control Mo-DC, although the suppressive effect of FR167653 was much less on BM-DC. These results indicate novel immunosuppressive properties of FR167653, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases through down-regulation of DC differentiation and maturation.
Nishimura
N
N
Third Department of Internal Medicine, The University of Tokushima, School of Medicine, Kuramoto-cho 3, Tokushima, Japan.
Nishioka
Y
Y
Shinohara
T
T
Tani
K
K
Sone
S
S
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000096:biosynthesis*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D018952:Antigens, CD34; D016207:Cytokines; C104334:FR 167653; D006131:Growth Inhibitors; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D011720:Pyrazoles; D011725:Pyridines