Fischer T C, Lauenstein H-D, Serowka F, Pilzner C, Groneberg D A, Welker P
Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, Free University and Humboldt University, Berlin, Germany.
Clin Exp Allergy. 2008 Jul;38(7):1168-73. doi: 10.1111/j.1365-2222.2008.02994.x. Epub 2008 May 8.
Neurotrophins such as nerve growth factor or brain-derived neurotrophic factor influence neuronal proliferation and differentiation via the low-affinity pan-neurotrophin receptor p75NTR that may play a pivotal role in linking the immune with the nervous system. Because the precise regulation of p75NTR gene transcription in mast cells under states of allergic inflammation has not been investigated in detail so far, the present studies assessed the gene regulation and expression of this receptor.
Transcriptional expression of p75NTR in human skin was studied in isolated cutaneous cells by means of RT-PCR. In situ lesional mast cell p75NTR expression was analysed by immunohistochemistry.
The p75NTR mRNA expression was found in isolated human skin mast cells and keratinocytes. Lower mRNA levels were present in fibroblasts and melanocytes but no transcripts were found in endothelial cells. The p75NTR protein expression was found in situ in lesional and non-lesional mast cells. A significantly increased expression of p75NTR protein was found in atopic dermatitis lesional mast cells when compared with control mast cell expression (P<0.05).
The demonstration of an increased level of p75NTR gene transcription in lesional mast cells points to an induction of low-affinity neurotrophin receptor sensitivity of mast cells under states of allergic inflammation. Topically administered neurotrophin receptor-modulating compounds may act as anti-inflammatory mediators in cutaneous allergic inflammation.
神经营养因子,如神经生长因子或脑源性神经营养因子,通过低亲和力泛神经营养因子受体p75NTR影响神经元的增殖和分化,该受体可能在连接免疫系统和神经系统方面发挥关键作用。由于迄今为止尚未详细研究过敏性炎症状态下肥大细胞中p75NTR基因转录的精确调控,因此本研究评估了该受体的基因调控和表达。
通过逆转录聚合酶链反应(RT-PCR)研究分离的皮肤细胞中p75NTR在人皮肤中的转录表达。通过免疫组织化学分析病变部位肥大细胞p75NTR的原位表达。
在分离的人皮肤肥大细胞和角质形成细胞中发现了p75NTR mRNA表达。成纤维细胞和黑素细胞中的mRNA水平较低,但在内皮细胞中未发现转录本。在病变部位和非病变部位的肥大细胞中均发现了p75NTR蛋白表达。与对照肥大细胞表达相比,特应性皮炎病变部位肥大细胞中p75NTR蛋白表达显著增加(P<0.05)。
病变部位肥大细胞中p75NTR基因转录水平升高表明,在过敏性炎症状态下肥大细胞的低亲和力神经营养因子受体敏感性增强。局部应用神经营养因子受体调节化合物可能作为皮肤过敏性炎症中的抗炎介质。