title: Extracellular signal-regulated kinase, stress-activated protein kinase/c-Jun N-terminal kinase, and p38mapk are involved in IL-10-mediated selective repression of TNF-alpha-induced activation and maturation of human peripheral blood monocyte-derived dendritic cells.
abstract: TNF-alpha or IL-10 has been implicated to reversibly regulate physiological states of dendritic cells (DCs). However, little is known about dual stimulations of these cytokines on DC properties and the intracellular signaling events that are responsible for the regulation of these states. Here, we show that a family of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase 2 (ERK2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38mapk, are potentially involved in IL-10-mediated selective suppression of TNF-alpha-induced changes of the monocyte-derived DC properties. TNF-alpha induced the cluster formation of the cells and the enhancement of cell surface expression levels of CD83, CD86, and HLA-DR, and T cell stimulatory capacity, whereas the capacities for the endocytosis and the chemotactic migration were suppressed in these cells. Treatment of monocyte-derived DCs with IL-10 resulted in the reduction of the cell surface expression levels of CD86, HLA-DR, and T cell stimulatory capacity, whereas both endocytic and chemotactic migratory capacities were increased by IL-10. Dual stimulations of monocyte-derived DCs with TNF-alpha and IL-10 selectively antagonized their respective effects on these DC properties. TNF-alpha induced tyrosine phosphorylation and enzymatic activation of ERK2, SAPK/JNK, and p38mapk, whereas IL-10 did not induce these events. Dual stimulations of TNF-alpha plus IL-10 abolished TNF-alpha-induced changes of these MAPKs in DCs. These results suggest that the blockage in the MAPKs cascades contributes to IL-10-mediated repression of TNF-alpha-induced changes of DC properties.
authors: Department of Cell Processing, Institute of Medical Science, University of Tokyo, Japan.
authors: K
authors: K
authors: Sato
authors: H
authors: H
authors: Nagayama
authors: K
authors: K
authors: Tadokoro
authors: T
authors: T
authors: Juji
authors: T A
authors: TA
authors: Takahashi
mesh_terms: D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D009000:Monocytes / Q000201:enzymology / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases