PMID- 17041145 OWN - NLM STAT- MEDLINE DCOM- 20070122 LR - 20221207 IS - 0953-8178 (Print) IS - 0953-8178 (Linking) VI - 18 IP - 12 DP - 2006 Dec TI - The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands. PG - 1729-36 AB - The endogenous anti-microbial peptide LL-37/hCAP-18 is an effector molecule of the innate host defense system at surfaces of the body. Besides its direct anti-microbial activity, the peptide interacts with different cell types. Dendritic cells (DCs) play a central role in mucosal host defense. It was the aim of the study to determine whether LL-37 modulates the response of DCs to pathogen-associated molecular patterns. Monocyte-derived DCs were stimulated with the Toll-like receptors (TLRs) ligands LPS, lipoteichoic acid and flagellin. We measured classical markers of DC maturation and assayed the ability of the DCs to activate T cell responses. Co-incubation with LL-37 resulted in suppressed activation of DCs. Levels of released IL-6, IL-12p70 and TNF-alpha and surface expression of HLA-DR, CD80, CD83, CD86 and the chemokine receptor CCR7 were decreased. Exposure of DCs to LL-37 during LPS exposure induced co-cultured naive T cells to produce less IL-2 and IFN-gamma and decreased their proliferation. The response of memory T cells to a recall antigen was also decreased. In conclusion, we demonstrate that the anti-microbial peptide LL-37 inhibits the activation of DCs by TLR ligands. We propose that LL-37 is a regulator of host defense responses at the intersection of innate and adaptive immune systems. FAU - Kandler, Kerstin AU - Kandler K AD - Department of Internal Medicine, Division for Pulmonary Diseases, Baldingerstrasse 1, 35043 Marburg, Germany. FAU - Shaykhiev, Renat AU - Shaykhiev R FAU - Kleemann, Peter AU - Kleemann P FAU - Klescz, Frank AU - Klescz F FAU - Lohoff, Michael AU - Lohoff M FAU - Vogelmeier, Claus AU - Vogelmeier C FAU - Bals, Robert AU - Bals R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061013 PL - England TA - Int Immunol JT - International immunology JID - 8916182 RN - 0 (Antimicrobial Cationic Peptides) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (Toll-Like Receptors) RN - 0 (Cathelicidins) SB - IM MH - Amino Acid Sequence MH - Antimicrobial Cationic Peptides/chemistry/*immunology MH - Cell Differentiation MH - Cells, Cultured MH - Dendritic Cells/cytology/*drug effects/*immunology MH - Humans MH - *Ligands MH - Lipopolysaccharides/immunology MH - Molecular Sequence Data MH - Monocytes/cytology/immunology MH - T-Lymphocytes/immunology MH - Toll-Like Receptors/*metabolism MH - Cathelicidins EDAT- 2006/10/17 09:00 MHDA- 2007/01/24 09:00 CRDT- 2006/10/17 09:00 PHST- 2006/10/17 09:00 [pubmed] PHST- 2007/01/24 09:00 [medline] PHST- 2006/10/17 09:00 [entrez] AID - dxl107 [pii] AID - 10.1093/intimm/dxl107 [doi] PST - ppublish SO - Int Immunol. 2006 Dec;18(12):1729-36. doi: 10.1093/intimm/dxl107. Epub 2006 Oct 13.