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Noga, O. et al.

O. Noga, M. Peiser, M. Altenähr, H. Knieling, R. Wanner, G. Hanf, R. Grosse, N. Suttorp,

Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor.

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.[1]

References

Differential activation of dendritic cells by nerve growth factor and brain-derived neurotrophic factor. Noga, O., Peiser, M., Altenähr, M., Knieling, H., Wanner, R., Hanf, G., Grosse, R., Suttorp, N. Clin. Exp. Allergy (2007) [Pubmed]

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