Activation of extracellular signal-related kinase by TNF-alpha controls the maturation and function of murine dendritic cells.
Functional roles of extracellular signal-related kinase (ERK) activation in dendritic-cell (DC) maturation have been unclear. In the present study, we investigated the ERK pathway in tumor necrosis factor (TNF)-alpha-induced maturation of murine spleen-derived DC. TNF-alpha increased surface expressions of major histocompatibility (MHC) and costimulatory molecules on DC in a dose-dependent manner. High (40 ng/ml) and low (0.4 ng/ml) concentrations of TNF-alpha markedly enhanced ERK1/2 activation in DC, and this activation was blocked completely by PD98059, a selective inhibitor of the ERK pathway. When DC were treated with TNF-alpha at a low but not a high concentration, PD98059 notably enhanced surface expressions of the MHC and costimulatory molecules and allostimulatory capability of the DC. Interleukin (IL)-12 production was enhanced significantly by PD98059 in DC treated with low or high concentration of TNF-alpha. These findings suggest that TNF-alpha-induced ERK activation negatively controls maturation and IL-12 production in murine DC.
Yanagawa
Yoshiki
Y
Division of Immunobiology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Iijima
Norifumi
N
Iwabuchi
Kazuya
K
Onoé
Kazunori
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one