Böhm Markus, Schiller Meinhard, Ständer Sonja, Seltmann Holger, Li Zhuo, Brzoska Thomas, Metze Dieter, Schiöth Helgi B, Skottner Anna, Seiffert Kristina, Zouboulis Christos C, Luger Thomas A
Department of Dermatology and Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Münster, Germany.
J Invest Dermatol. 2002 Mar;118(3):533-9. doi: 10.1046/j.0022-202x.2001.01704.x.
Many lines of evidence indicate that the activity of sebaceous glands can be modulated by neuropeptides. Direct evidence in man, however, is still missing. We show that SZ95 sebocytes, an immortalized human sebaceous gland cell line, express receptors for alpha-melanocyte-stimulating hormone. Reverse transcription polymerase chain reaction with primers against the five melanocortin receptors and immunofluorescence studies using an antibody directed against a peptide corresponding to the amino acids 2-18 of the human melanocortin-1 receptor disclosed specific transcripts and immunoreactivity for melanocortin-1 receptor in these cells. Melanocortin-1 receptor expression was confirmed in sebocytes of normal human skin by immunohistochemistry. In contrast, no immunostaining for the melanocortin-5 receptor could be detected in sebocytes in situ, in accordance with the lack of specific transcripts for this melanocortin receptor in SZ95 sebocytes. As cytokines play an important role in the recruitment of inflammatory cells in acne and related disorders and alpha-melanocyte-stimulating hormone exerts immunomodulatory effects in many other cell types, we investigated the effect of alpha-melanocyte-stimulating hormone on interleukin-8 secretion by SZ95 sebocytes. Treatment with interleukin-1beta resulted in a marked increase in interleukin-8 release that was partially blocked by coincubation with alpha-melanocyte-stimulating hormone in a dose-dependent manner. Taken together, we show here that the melanocortin-1 receptor is expressed in vitro and in situ in human sebocytes. By modulating interleukin-8 secretion, alpha-melanocyte-stimulating hormone may act as a modulator of inflammatory responses in the pilosebaceous unit.
许多证据表明,皮脂腺的活性可受神经肽调节。然而,人类的直接证据仍然缺失。我们发现,永生化的人皮脂腺细胞系SZ95皮脂腺细胞表达α-黑素细胞刺激素受体。使用针对五种黑皮质素受体的引物进行逆转录聚合酶链反应,以及使用针对与人黑素皮质素-1受体氨基酸2-18对应的肽段的抗体进行免疫荧光研究,均揭示了这些细胞中黑素皮质素-1受体的特异性转录本和免疫反应性。通过免疫组织化学在正常人皮肤的皮脂腺细胞中证实了黑素皮质素-1受体的表达。相比之下,根据SZ95皮脂腺细胞中该黑皮质素受体缺乏特异性转录本,原位皮脂腺细胞中未检测到黑素皮质素-5受体的免疫染色。由于细胞因子在痤疮及相关疾病中炎症细胞的募集中起重要作用,且α-黑素细胞刺激素在许多其他细胞类型中发挥免疫调节作用,我们研究了α-黑素细胞刺激素对SZ95皮脂腺细胞白细胞介素-8分泌的影响。用白细胞介素-1β处理导致白细胞介素-8释放显著增加,而与α-黑素细胞刺激素共同孵育可部分剂量依赖性地阻断这种增加。综上所述,我们在此表明黑素皮质素-1受体在人皮脂腺细胞中体外和原位均有表达。通过调节白细胞介素-8的分泌,α-黑素细胞刺激素可能作为毛囊皮脂腺单位炎症反应的调节剂。