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Pro-inflammatory cytokines upregulate the skin immunoreactivity for NGF, NT-3, NT-4 and their receptor, p75NTR in vivo: a preliminary report

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Abstract

Skin and hair follicles are both source and target of various cytokines and neurotrophins (NTs). While several pro-inflammatory cytokines are recognized to alter the expression of NTs and their receptors (NTRs), for example, on brain cells and fibroblasts in vitro, it is unknown whether this also occurs in normal mammalian skin in vivo. As a first step toward exploring this, we studied in murine back skin (C57BL/6) whether intradermally injected interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) altered the cutaneous immunoreactivity patterns of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4), Trk-A, Trk-B, Trk-C and p75NTR and their receptors (TrkA, TrkB, TrkC, p75NTR) on the protein level in situ. By immunohistology, IFNγ, IL-1β, and TNF-α as well as a cocktail of all three cytokines increased NGF immunoreactivity (IR) in the proximal outer root sheath and hair matrix of anagen VI pelage hair follicles. The cytokine cocktail upregulated NT-3 and NT-4 IR in the epidermis, increased NT-4 IR in selected cells of the proximal outer root sheath, and also enhanced IR of p75NTR, in the follicular dermal papilla. Therefore, this pilot study provides the first preliminary indications that proinflammatory cytokines upregulate the cutaneous immunoreactivity of NGF, NT-3, NT-4 and their receptor p75NTR in vivo. This raises the question to which extent several of the recognized cutaneous effects of IFNγ, IL-1β and TNF-α are mediated indirectly via modulating the expression of selected NTs and/or NTRs.

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Acknowledgements

The authors thank Kimberly Rosegger for editing the manuscript and Sabine Lewandowski for her help with digital image processing. This study was supported in part by grants from the Deutsche Forschungsgemeinschaft to RP (Pa 345/6–4) and SH (SFB507B11).

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Eppendorf, Hamburg University, Martinistraße 52, 20246, Hamburg, Germany

    Holger Bläsing & Ralf Paus

  2. Center for Anatomy, Institute of Cell Biology and Neurobiology, Charité University Hospital, Schumannstr. 20-21, 10098, Berlin, Germany

    Sven Hendrix

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  1. Holger Bläsing
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  2. Sven Hendrix
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  3. Ralf Paus
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Correspondence to Ralf Paus.

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Holger Bläsing and Sven Hendrix have contributed equally

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Bläsing, H., Hendrix, S. & Paus, R. Pro-inflammatory cytokines upregulate the skin immunoreactivity for NGF, NT-3, NT-4 and their receptor, p75NTR in vivo: a preliminary report. Arch Dermatol Res 296, 580–584 (2005). https://doi.org/10.1007/s00403-005-0563-y

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