Extracellular signal-regulated kinase, stress-activated protein kinase c-Jun N-terminal kinase, and p38(mapk) are involved in IL-10-mediated selective repression of TNF-alpha-induced activation and maturation of human peripheral blood monocyte-derived dendritic cells

TNF-alpha or IL-10 has been implicated to reversibly regulate physiological states of dendritic cells (DCs). However, little is known about dual stimu lations of these cytokines on DC properties and the intracellular signaling events that are responsible for the regulation of these states, Here, we s how that a family of mitogen-activated protein kinases (MAPKs), extracellul ar signal-regulated kinase 2 (ERK2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and p38(mapk), are potentially involved in IL -10-mediated selective suppression of TNF-alpha-induced changes of the mono cyte-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 t he cell surface expression levels of CD86, HLA-DR, and T cell stimulatory c apacity, whereas both endocytic and chemotactic migratory capacities were i ncreased by IL-10, Dual stimulations of monocyte-derived DCs with TNF-alpha and IL-10 selectively antagonized their respective effects on these DC pro perties, TNF-alpha induced tyrosine phosphorylation and enzymatic activatio n of ERK2, SAPK/JNK, and p38(mapk), whereas IL-10 did not induce these even ts. Dual stimulations of TNF-alpha plus IL-10 abolished TNF-alpha-induced c hanges of these MAPKs in DCs, These results suggest that the blockage in th e MAPKs cascades contributes to IL-10-mediated repression of TNF-alpha-indu ced changes of DC properties.