PMID- 17845420 OWN - NLM STAT- MEDLINE DCOM- 20071016 LR - 20070911 IS - 0954-7894 (Print) IS - 0954-7894 (Linking) VI - 37 IP - 9 DP - 2007 Sep TI - Cell type-specific regulation of brain-derived neurotrophic factor in states of allergic inflammation. PG - 1386-91 AB - 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. FAU - Groneberg, D A AU - Groneberg DA AD - Institute of Occupational Medicine, Charite- Universitatsmedizin Berlin, Free University and Humboldt University, Berlin, Germany. groneberg.david@mh-hannover.de FAU - Fischer, T C AU - Fischer TC FAU - Peckenschneider, N AU - Peckenschneider N FAU - Noga, O AU - Noga O FAU - Dinh, Q T AU - Dinh QT FAU - Welte, T AU - Welte T FAU - Welker, P AU - Welker P LA - eng PT - Journal Article 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 (Brain-Derived Neurotrophic Factor) SB - IM MH - Adult MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Case-Control Studies MH - Dermatitis, Atopic/*immunology MH - Down-Regulation MH - Female MH - Humans MH - Immunohistochemistry MH - Male MH - Mast Cells/*immunology MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2007/09/12 09:00 MHDA- 2007/10/17 09:00 CRDT- 2007/09/12 09:00 PHST- 2007/09/12 09:00 [pubmed] PHST- 2007/10/17 09:00 [medline] PHST- 2007/09/12 09:00 [entrez] AID - CEA2790 [pii] AID - 10.1111/j.1365-2222.2007.02790.x [doi] PST - ppublish SO - Clin Exp Allergy. 2007 Sep;37(9):1386-91. doi: 10.1111/j.1365-2222.2007.02790.x.