PMID- 21183242 OWN - NLM STAT- MEDLINE DCOM- 20110902 LR - 20181201 IS - 1878-3279 (Electronic) IS - 0171-2985 (Linking) VI - 216 IP - 6 DP - 2011 Jun TI - Dendritic cells matured by a prostaglandin E2-containing cocktail can produce high levels of IL-12p70 and are more mature and Th1-biased than dendritic cells treated with TNF-alpha or LPS. PG - 649-62 LID - 10.1016/j.imbio.2010.11.004 [doi] AB - Dendritic cells (DCs) play a crucial role in the initiation of an immune response. As maturation is critical for effective antigen presentation, different methods have been used to generate mature DCs (mDCs) ex vivo. The use of a maturation cocktail (MC) consisting of IL-1beta, IL-6, TNF-alpha, and prostaglandin E2 (PGE2) initially showed promising results, but then was challenged because of low production of IL-12p70 and the potential for induction of Th2-type immune responses. To investigate this contention, we compared two of the most commonly used maturation factors, TNF-alpha and LPS, with MC. Maturation cocktail was superior to TNF-alpha and LPS with respect to enhancement of mDC-specific surface marker expression (CD83, CD86, and HLA-DR), induction of T cell proliferation by mDCs, and directional motility of mDCs toward CCL19. These results were supported by increased expression of a significant number of additional maturation-related genes by MC in comparison to TNF-alpha and LPS. In addition, we did not observe a Th2-biased shift in the gene expression profile of mDCs generated by MC. Conversely, MC induced more Th1-promoting transcriptional changes than LPS or TNF-alpha, including increased transcript levels of Th1-type cytokines such as IL-15, IL-12beta, and EBI3 (IL-27beta) and MHC class I molecules, Th1-promoting changes in the transcripts of CXCL16, CCL13, and CCL18, and reduced transcript levels of MHC class II molecules. More interestingly, the Th1-promoting characteristics of MC-mDCs were confirmed by their potential to produce large amounts of IL-12p70 after effective stimulation simulating in vivo events. CI - Copyright (c) 2010 Elsevier GmbH. All rights reserved. FAU - Landi, Abdolamir AU - Landi A AD - Vaccine and Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Rd, Saskatoon, SK S7N5E3, Canada. FAU - Babiuk, Lorne A AU - Babiuk LA FAU - van Drunen Littel-van den Hurk, Sylvia AU - van Drunen Littel-van den Hurk S LA - eng GR - Canadian Institutes of Health Research/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101125 PL - Netherlands TA - Immunobiology JT - Immunobiology JID - 8002742 RN - 0 (Adjuvants, Immunologic) RN - 0 (Lipopolysaccharides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 187348-17-0 (Interleukin-12) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - Adult MH - Cells, Cultured MH - Culture Techniques/*methods MH - Dendritic Cells/cytology/*drug effects/*immunology MH - Dinoprostone/*pharmacology MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation/drug effects/immunology MH - Humans MH - Interleukin-12/metabolism MH - Lipopolysaccharides/*pharmacology MH - Male MH - Th1 Cells/cytology/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology MH - Young Adult EDAT- 2010/12/25 06:00 MHDA- 2011/09/03 06:00 CRDT- 2010/12/25 06:00 PHST- 2010/07/06 00:00 [received] PHST- 2010/11/11 00:00 [revised] PHST- 2010/11/17 00:00 [accepted] PHST- 2010/12/25 06:00 [entrez] PHST- 2010/12/25 06:00 [pubmed] PHST- 2011/09/03 06:00 [medline] AID - S0171-2985(10)00215-9 [pii] AID - 10.1016/j.imbio.2010.11.004 [doi] PST - ppublish SO - Immunobiology. 2011 Jun;216(6):649-62. doi: 10.1016/j.imbio.2010.11.004. Epub 2010 Nov 25.