PMID- 17892512 OWN - NLM STAT- MEDLINE DCOM- 20080115 LR - 20171116 IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 37 IP - 11 DP - 2007 Nov TI - Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor. PG - 1701-8 AB - BACKGROUND: Neurotrophins are involved in inflammatory reactions influencing several cells in health and disease including allergy and asthma. Dendritic cells (DCs) play a major role in the induction of inflammatory processes with an increasing role in allergic diseases as well. OBJECTIVE: The aim of this study was to investigate the influence of neurotrophins on DC function. METHODS: Monocyte-derived dendritic cells were generated from allergic and non-allergic donors. Neurotrophin receptors were demonstrated by western blotting, flow cytometry and fluorescence microscopy. Activation of small GTPases was evaluated by pull-down assays. DCs were incubated with nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and supernatants were collected for measurement of IL-4, IL-6, IL-10, IL-12p70, TNF-alpha and TGF-beta. RESULTS: Receptor proteins were detectable by western blot, fluorescence activated cell sorting analysis and fluorescence microscopy. Signalling after neurotrophin stimulation occurred in a ligand-specific pattern. NGF led to decreased RhoA and increased Rac activation, while BDNF affected RhoA and Rac activity in a reciprocal fashion. Cells of allergics released a significantly increased amount of IL-6, while for healthy subjects a significantly higher amount of IL-10 was found. CONCLUSION: These data indicate that DCs are activated by the neurotrophins NGF and BDNF by different pathways in a receptor-dependant manner. These cells then may initiate inflammatory responses based on allergic sensitization releasing preferred cytokines inducing tolerance or a T-helper type 2 response. FAU - Noga, O AU - Noga O AD - Department of Infectious and Respiratory Diseases; Charite, Universitatsmedizin Berlin, Berlin, Germany. oliver.noga@charite.de FAU - Peiser, M AU - Peiser M FAU - Altenahr, M AU - Altenahr M FAU - Knieling, H AU - Knieling H FAU - Wanner, R AU - Wanner R FAU - Hanf, G AU - Hanf G FAU - Grosse, R AU - Grosse R FAU - Suttorp, N AU - Suttorp N LA - eng PT - Journal Article DEP - 20070924 PL - England TA - Clin Exp Allergy JT - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JID - 8906443 RN - 0 (Antigens, CD) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 130068-27-8 (Interleukin-10) RN - 147205-72-9 (CD40 Ligand) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 3.6.5.2 (rac GTP-Binding Proteins) RN - EC 3.6.5.2 (rho GTP-Binding Proteins) RN - O84C90HH2L (Poly I-C) SB - IM MH - Antigens, CD/metabolism MH - Blotting, Western MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - CD40 Ligand/pharmacology MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Cytokines/pharmacology MH - Dendritic Cells/cytology/*drug effects/metabolism MH - Dose-Response Relationship, Drug MH - Flow Cytometry MH - Gene Expression/drug effects MH - Humans MH - Hypersensitivity/blood MH - Interleukin-10/metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides/pharmacology MH - Monocytes/cytology/drug effects/metabolism MH - Nerve Growth Factor/*pharmacology MH - Poly I-C/pharmacology MH - Receptor, trkA/genetics/metabolism MH - Receptor, trkB/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - T-Lymphocytes/cytology/drug effects/metabolism MH - rac GTP-Binding Proteins/metabolism MH - rho GTP-Binding Proteins/metabolism EDAT- 2007/09/26 09:00 MHDA- 2008/01/16 09:00 CRDT- 2007/09/26 09:00 PHST- 2007/09/26 09:00 [pubmed] PHST- 2008/01/16 09:00 [medline] PHST- 2007/09/26 09:00 [entrez] AID - CEA2832 [pii] AID - 10.1111/j.1365-2222.2007.02832.x [doi] PST - ppublish SO - Clin Exp Allergy. 2007 Nov;37(11):1701-8. doi: 10.1111/j.1365-2222.2007.02832.x. Epub 2007 Sep 24.