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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/11773

Title: Nerve Growth Factor Partially Recovers Inflamed Skin from Stress-Induced Worsening in Allergic Inflammation
Authors: Peters, Eva M. J.
Liezmann, Christiane
Spatz, Katharina
Daniltchenko, Maria
Joachim, Ricarda
Gimenez-Rivera, Andrey
Botchkarev, Vladimir A.
Brandner, Johanna M.
Klapp, Burghard F.
Issue Date: 2011
Abstract: Neuroimmune dysregulation characterizes atopic disease, but its nature and clinical impact remain ill-defined. Induced by stress, the neurotrophin nerve growth factor (NGF) may worsen cutaneous inflammation. We therefore studied the role of NGF in the cutaneous stress response in a mouse model for atopic dermatitis-like allergic dermatitis (AlD). Combining several methods, we found that stress increased cutaneous but not serum or hypothalamic NGF in telogen mice. Microarray analysis showed increased mRNAs of inflammatory and growth factors associated with NGF in the skin. In stress-worsened AlD, NGF-neutralizing antibodies markedly reduced epidermal thickening together with NGF, neurotrophin receptor (tyrosine kinase A and p75 neurotrophin receptor), and transforming growth factor-beta expression by keratinocytes but did not alter transepidermal water loss. Moreover, NGF expression by mast cells was reduced; this corresponded to reduced cutaneous tumor necrosis factor-alpha (TNF-alpha) mRNA levels but not to changes in mast cell degranulation or in the T helper type 1 (Th1)/Th2 cytokine balance. Also, eosinophils expressed TNF receptor type 2, and we observed reduced eosinophil infiltration after treatment with NGF-neutralizing antibodies. We thus conclude that NGF acts as a local stress mediator in perceived stress and allergy and that increased NGF message contributes to worsening of cutaneous inflammation mainly by enhancing epidermal hyperplasia, pro-allergic cytokine induction, and allergy-characteristic cellular infiltration.
Notes: [Peters, Eva M. J.; Liezmann, Christiane; Spatz, Katharina; Daniltchenko, Maria; Joachim, Ricarda; Gimenez-Rivera, Andrey; Klapp, Burghard F.] Charite, Charite Ctr Internal Med & Dermatol CC12 12, Dept Psychosomat, Neurosci Res Ctr, D-10117 Berlin, Germany. [Hendrix, Sven] Hasselt Univ, Dept Morphol, Hasselt, Belgium. [Hendrix, Sven] Hasselt Univ, BIOMED, Hasselt, Belgium. [Botchkarev, Vladimir A.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Brandner, Johanna M.] Univ Hosp Hamburg Eppendorf, Dept Dermatol & Venerol, Hamburg, Germany. eva.peters@charite.de
URI: http://hdl.handle.net/1942/11773
DOI: 10.1038/jid.2010.317
ISI #: 000287229700027
ISSN: 0022-202X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2012
Appears in Collections: Research publications

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