Toyoda Masahiko, Nakamura Motokazu, Morohashi Masaaki
Department of Dermatology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyoma 930-0194, Japan.
Eur J Dermatol. 2002 Sep-Oct;12(5):422-7.
This review provides a new insight into the participation of neuropeptides, notably substance P (SP), in the pathophysiology of acne. We show morphological alterations of sebaceous glands elicited by SP and differences in expression of various neurogenic factors in association with sebaceous glands in acne-prone versus normal facial skin. In vitro studies reveal that SP promotes both the proliferation and the differentiation of sebaceous glands. SP induces the expression of neutral endopeptidase, a potent neuropeptide-degrading enzyme, in sebaceous germinative cells and of E-selectin by perisebaceous venules. Facial skin from acne patients is characterized by rich innervation, by increased numbers of SP-containing nerves and mast cells, and by strong expression of neutral endopeptidase in sebaceous glands and E-selectin in venules around sebaceous glands, compared with normal skin. Mast cell-derived IL-6 and TNF-alpha, followed by SP-stimulated degranulation, have the potential to induce nerve growth factor expression by sebaceous cells which results in the promotion of innervation and in the expression of E-selectin, respectively. SP enhances mast cell proliferation through up-regulation of stem cell factor expression in fibroblasts. These findings suggest the involvement of neurogenic factors, such as neuropeptides, in the disease process of acne and explain the possible mechanism of the exacerbation of acne from a neurological point of view.
本综述为神经肽尤其是P物质(SP)参与痤疮的病理生理学提供了新的见解。我们展示了SP引起的皮脂腺形态学改变,以及在易长痤疮的面部皮肤与正常面部皮肤中,与皮脂腺相关的各种神经源性因子表达的差异。体外研究表明,SP既能促进皮脂腺的增殖,也能促进其分化。SP可诱导皮脂腺生发细胞中一种强效神经肽降解酶——中性内肽酶的表达,并可诱导皮脂腺周围小静脉表达E-选择素。与正常皮肤相比,痤疮患者的面部皮肤具有神经支配丰富、含SP神经和肥大细胞数量增加、皮脂腺中中性内肽酶和皮脂腺周围小静脉中E-选择素表达强烈的特征。肥大细胞衍生的白细胞介素-6和肿瘤坏死因子-α,随后是SP刺激的脱颗粒,有可能分别诱导皮脂腺细胞表达神经生长因子,从而促进神经支配和E-选择素的表达。SP通过上调成纤维细胞中干细胞因子的表达来增强肥大细胞增殖。这些发现表明神经源性因子如神经肽参与了痤疮的疾病过程,并从神经学角度解释了痤疮加重的可能机制。