PMID- 22784440 OWN - NLM STAT- MEDLINE DCOM- 20130704 LR - 20181202 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 218 IP - 2 DP - 2013 Feb TI - Maturation of human iDCs by IL-18 plus PGE2, but not by each stimulus alone, induced migration toward CCL21 and the secretion of IL-12 and IFN-gamma. PG - 238-44 LID - S0171-2985(12)00098-8 [pii] LID - 10.1016/j.imbio.2012.05.003 [doi] AB - Dendritic cells (DCs) are potent antigen-presenting cells that initiate the primary immune response and whose functional properties in vivo depend on the maturation stimulus. We describe the functional properties of human monocyte-derived DCs after the maturation of immature DCs (iDCs) for 2 days with LPS (100 ng/ml), PGE2 (1 mug/ml), CD40L (1 mug/ml) or IL-18 (200 ng/ml) and with CD40L+PGE2 and IL-18+PGE2 mixtures at the same concentrations as above. Neither IL-18 nor PGE2 alone stimulated IL-12 or IFN-gamma secretion. When administered simultaneously to 1x10(6)iDCs/ml, IL-18+PGE2 induced the secretion of 131.4+/-6.7 pg IL-12/ml and 355+/-87 pg IFN-gamma/ml but there was no detectable IL-10 secretion. However, PGE2 alone stimulated the secretion of 208+/-89 pg IL-10/ml whereas IL-18 alone did not stimulate the secretion of IL-10, IL-12, TNF-alpha or INF-gamma. When the mixture of CD40L+PGE2 was used, only migration toward CCL19 and CCL21 was induced. CD40L did not stimulate the secretion of IL-10, IL-12, TNF-alpha or IFN-gamma and did not stimulate migration toward CCL19 or CCL21. The extent of stimulation of T cell proliferation was essentially the same for all stimuli at the concentrations given above. New properties such as IL-12 and INF-gamma secretion and migration toward CCL21 emerged when a mixture of IL-18+PGE2 was employed. These data show that when the pairs of stimuli reported here were used simultaneously their effect was not additive. This system can be used to prepare mDCs with properties useful for cell therapy and also as a model to investigate the mechanisms of cytokine secretion and cell migration. CI - Copyright (c) 2012 Elsevier GmbH. All rights reserved. FAU - da Silva, Idalete AU - da Silva I AD - Departamento de Biologia Celular e Molecular e Bioagentes Patogenicos e Centro de Quimica de Proteinas, Brazil. FAU - Gomes, Glauce G AU - Gomes GG FAU - Menezes, Camila C B O AU - Menezes CC FAU - Palma, Patricia V B AU - Palma PV FAU - Orellana, Maristela D AU - Orellana MD FAU - Covas, Dimas T AU - Covas DT FAU - Chammas, Roger AU - Chammas R FAU - Greene, Lewis J AU - Greene LJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120511 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Chemokine CCL19) RN - 0 (Chemokine CCL21) RN - 0 (Interleukin-18) RN - 0 (Lipopolysaccharides) RN - 147205-72-9 (CD40 Ligand) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - CD40 Ligand/immunology MH - Cell Differentiation MH - Cell Movement/immunology MH - Cell Proliferation MH - Cells, Cultured MH - Chemokine CCL19/metabolism MH - Chemokine CCL21/*metabolism MH - Dendritic Cells/*immunology/pathology MH - Dinoprostone/*immunology MH - Humans MH - Interferon-gamma/metabolism MH - Interleukin-12/metabolism MH - Interleukin-18/*immunology MH - Lipopolysaccharides/immunology MH - Lymphocyte Activation MH - Monocytes/pathology MH - Receptor Cross-Talk MH - T-Lymphocytes/*immunology EDAT- 2012/07/13 06:00 MHDA- 2013/07/05 06:00 CRDT- 2012/07/13 06:00 PHST- 2011/04/07 00:00 [received] PHST- 2012/05/07 00:00 [accepted] PHST- 2012/07/13 06:00 [entrez] PHST- 2012/07/13 06:00 [pubmed] PHST- 2013/07/05 06:00 [medline] AID - S0171-2985(12)00098-8 [pii] AID - 10.1016/j.imbio.2012.05.003 [doi] PST - ppublish SO - Immunobiology. 2013 Feb;218(2):238-44. doi: 10.1016/j.imbio.2012.05.003. Epub 2012 May 11.