PMID- 15313427 OWN - NLM STAT- MEDLINE DCOM- 20050223 LR - 20141120 IS - 1567-5769 (Print) IS - 1567-5769 (Linking) VI - 4 IP - 10-11 DP - 2004 Oct TI - Triacyl-lipopentapeptide adjuvants: TLR2-dependent activation of macrophages and modulation of receptor-mediated cell activation by altering acyl-moieties. PG - 1287-300 AB - Synthetic lipopeptides derived from bacterial lipoprotein are efficient immunoadjuvants. In vitro they activate antigen presenting cells (APCs) to induce the translocation of nuclear factor kappa B (NF-kappaB) and the activation of further transcription factors. This results in the expression of genes encoding cytokines such as IL-1, IL-6, TNF-alpha and in the release of reactive oxygen/nitrogen intermediates. The molecular structure of microbial products determines TLR specificity and thus their activatory potential and immunoadjuvanticity. In the present study, we investigated the lipopeptide-induced activation of leukocytes at different cellular levels by applying derivatives of a synthetic lipopentapeptide-fatty acid library. Our results show that TLR2 plays a key role for the activation of bone marrow-derived macrophages (BMDMs) by lipopentapeptide derivatives and that the fatty acid composition of the lipopeptides determines their activation potential and TLR specificity. FAU - Muller, Silke D C AU - Muller SD AD - Institut fur Molekulare Medizin und Zellforschung der Universitat, AK Tumorimmunologie/Vakzine, Stefan-Meier-Str. 8, D-79104 Freiburg, Germany. FAU - Muller, Markus R AU - Muller MR FAU - Huber, Maria AU - Huber M FAU - Esche Uv, Ulrich v d AU - Esche Uv Uv FAU - Kirschning, Carsten J AU - Kirschning CJ FAU - Wagner, H AU - Wagner H FAU - Bessler, Wolfgang G AU - Bessler WG FAU - Mittenbuhler, Klaus AU - Mittenbuhler K LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Adjuvants, Immunologic) RN - 0 (Bacterial Proteins) RN - 0 (Fatty Acids, Unsaturated) RN - 0 (Lipoproteins) RN - 0 (Membrane Glycoproteins) RN - 0 (NF-kappa B) RN - 0 (Peptide Library) RN - 0 (Peptides) RN - 0 (Receptors, Cell Surface) RN - 0 (TLR2 protein, human) RN - 0 (Tlr2 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptors) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) SB - IM MH - Adjuvants, Immunologic/chemistry/*pharmacology MH - Animals MH - Bacterial Proteins/chemistry MH - Cell Line MH - Extracellular Signal-Regulated MAP Kinases/metabolism MH - Fatty Acids, Unsaturated/*chemistry MH - Humans MH - In Vitro Techniques MH - Lipoproteins/*chemistry MH - Macrophage Activation/genetics/*physiology MH - Macrophages/*metabolism MH - Membrane Glycoproteins/genetics/physiology MH - Mice MH - Mice, Inbred C57BL MH - NF-kappa B/metabolism MH - Nitric Oxide/metabolism MH - Peptide Library MH - Peptides/chemistry/*pharmacology MH - Phosphorylation MH - Receptors, Cell Surface/genetics/*physiology MH - Toll-Like Receptor 2 MH - Toll-Like Receptors MH - Transfection EDAT- 2004/08/18 05:00 MHDA- 2005/02/24 09:00 CRDT- 2004/08/18 05:00 PHST- 2003/09/11 00:00 [received] PHST- 2004/02/04 00:00 [revised] PHST- 2004/04/22 00:00 [accepted] PHST- 2004/08/18 05:00 [pubmed] PHST- 2005/02/24 09:00 [medline] PHST- 2004/08/18 05:00 [entrez] AID - S1567576904001420 [pii] AID - 10.1016/j.intimp.2004.04.012 [doi] PST - ppublish SO - Int Immunopharmacol. 2004 Oct;4(10-11):1287-300. doi: 10.1016/j.intimp.2004.04.012.