Groneberg D A, Fischer T C, Peckenschneider N, Noga O, Dinh Q T, Welte T, Welker P
Institute of Occupational Medicine, Charité- Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany.
Clin Exp Allergy. 2007 Sep;37(9):1386-91. doi: 10.1111/j.1365-2222.2007.02790.x.
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.
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.
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.
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.
脑源性神经营养因子（BDNF）是一种影响神经元增殖和分化的分子。在过敏状态下，它可能通过将免疫系统与神经系统联系起来协调炎症变化。由于肥大细胞（MCs）中基因转录的精确调控尚不清楚，本研究评估了这种炎症细胞类型中BDNF的基因调控。
使用逆转录聚合酶链反应（RT-PCR）在分离的细胞中研究人皮肤中BDNF的转录表达。通过免疫组织化学分析病变部位MCs中BDNF蛋白的原位表达，并与MCs的差异染色以及BDNF对HaCaT角质形成细胞的功能作用相关联。
在分离的人皮肤MCs、角质形成细胞和成纤维细胞中发现了BDNF mRNA表达。此外，在内皮细胞和黑素细胞中也发现了低水平表达。在病变部位和非病变部位的MCs中均发现了BDNF蛋白的原位表达。与对照MCs表达相比，特应性皮炎病变部位的MCs中BDNF蛋白表达显著降低。体外功能实验表明，BDNF刺激的减少导致HaCaT角质形成细胞中干细胞因子和白细胞介素-8的分泌率增加。
病变部位MCs中BDNF基因转录水平降低的证明表明，皮肤过敏性炎症中MCs释放的神经营养因子存在差异调节。局部应用的神经营养因子受体调节化合物应具有受体靶点特异性，而不是在特应性皮炎或过敏性哮喘等疾病中普遍起作用。
