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Related Collections Immunobiology Phagocytes Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 96 No. 3 (August 1), 2000: pp. 1039-1046 The PI3 kinase, p38 SAP kinase, and NF-B signal transduction pathways are involved in the survival and maturation of lipopolysaccharide-stimulated human monocyte-derived dendritic cells Kirit M. Ardeshna, Arnold R. Pizzey, Stephen Devereux, and Asim Khwaja From the Department of Haematology, Royal Free and University College Medical School, London, United Kingdom. As a dendritic cell (DC) matures, it becomes more potent as an antigen-presenting cell. This functional change is accompanied by a change in DC immunophenotype. The signal transduction events underlying this process are poorly characterized. In this study, we have investigated the signal transduction pathways involved in the lipopolysaccharide (LPS)-induced maturation of human monocyte-derived DCs (MoDCs) in vitro. We show that exposure of immature MoDCs to LPS activates the p38 stress-activated protein kinase (p38SAPK), extracellular signal-regulated protein kinase (ERK), phosphoinositide 3-OH kinase (PI3 kinase)/Akt, and nuclear factor (NF)-B pathways. Studies using inhibitors demonstrate that PI3 kinase/Akt but not the other pathways are important in maintaining survival of LPS-stimulated MoDCs. Inhibiting p38SAPK prevented activation of the transcription factors ATF-2 and CREB and significantly reduced the LPS-induced up-regulation of CD80, CD83, and CD86, but did not have any significant effect on the LPS-induced changes in macropinocytosis or HLA-DR, CD40, and CD1a expression. Inhibiting the NF-B pathway significantly reduced the LPS-induced up-regulation of HLA-DR as well as CD80, CD83, and CD86. Inhibiting the p38SAPK and NF-B pathways simultaneously had variable effects depending on the cell surface marker studied. It thus appears that different aspects of LPS-induced MoDC maturation are regulated by different and sometimes overlapping pathways. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. K. Choi, Y. H. Kim, P. M. Kwon, S. C. Lee, S. W. Kang, M. S. Kim, M. J. Lee, and B. S. Kwon 4-1BB Functions As a Survival Factor in Dendritic Cells J. Immunol., April 1, 2009; 182(7): 4107 - 4115. [Abstract] [Full Text] [PDF] M. Ahlmann, G. Varga, K. Sturm, R. Lippe, K. Benedyk, D. Viemann, T. Scholzen, J. Ehrchen, F. U. Muller, M. Seidl, et al. The Cyclic AMP Response Element Modulator {alpha} Suppresses CD86 Expression and APC Function J. Immunol., April 1, 2009; 182(7): 4167 - 4174. [Abstract] [Full Text] [PDF] B. M. Janelsins, A. R. Mathers, O. A. Tkacheva, G. Erdos, W. J. Shufesky, A. E. 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