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Cell type-specific regulation of brain-derived neurotrophic factor in states of allergic inflammation

Authors

  • D. A. Groneberg,

    1. Institute of Occupational Medicine, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany,
    2. Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany,
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    • 1Contributed equally to this work.

  • T. C. Fischer,

    1. Department of Dermatology and Allergy, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany,
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    • 1Contributed equally to this work.

  • N. Peckenschneider,

    1. Department of Dermatology and Allergy, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany,
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  • O. Noga,

    1. Department of Medicine/Psychosomatics, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany
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  • Q. T. Dinh,

    1. Department of Medicine/Psychosomatics, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany
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  • T. Welte,

    1. Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany,
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  • P. Welker

    1. Institute of Anatomy, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany
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Correspondence:
David A. Groneberg, Institute of Occupational Medicine, Charité– Universitätsmedizin Berlin, Free University and Humboldt University, Augustenburger Platz 1 OR-1, D-13353 Berlin, Germany. E-mail: groneberg.david@mh-hannover.de

Summary

Background Brain-derived neurotrophic factor (BDNF) is a molecule influencing neuronal proliferation and differentiation. In states of allergy, it may orchestrate inflammatory changes by linking the immune system with the nervous system. Because the precise regulation of gene transcription in mast cells MCs is not clear, the present studies assessed the gene regulation of BDNF in this inflammatory cell type.

Methods Transcriptional expression of BDNF in human skin was studied in isolated cells using RT-PCR. In situ lesional MC BDNF protein expression was analysed by immunohistochemistry and related to the differential staining of MCs and functional effects of BDNF on HaCaT keratinocytes.

Results BDNF mRNA expression was found in isolated human skin MCs, keratinocytes, and fibroblasts. Also, low levels were found in endothelial cells and melanocytes. BDNF protein expression was found in situ in lesional and non-lesional MCs. A significantly decreased expression of BDNF protein was found in atopic dermatitis lesional MCs when compared with control MC expression. Functional in vitro experiments demonstrated that a decrease in BDNF stimulation led to increased secretion rates for stem cell factor and IL-8 in HaCaT keratinocytes.

Conclusion The demonstration of a decreased level of BDNF gene transcription in lesional MCs points to a differential regulation of MC-released neutrotrophins in cutaneous allergic inflammation. Topically administered neurotrophin receptor-modulating compounds should be receptor target specific and not universally acting in diseases such as atopic dermatitis or allergic asthma.

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