Department of Instrumental Analysis, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia in Katowice, Sosnowiec, Poland.
Exp Dermatol. 2019 May;28(5):551-560. doi: 10.1111/exd.13908. Epub 2019 Mar 19.
Increasing evidence suggests that human epidermal melanocytes play an important role in the skin immune system; however, a role of their pigmentation in immune and inflammatory responses is poorly examined. In the study, the expression of Toll-like receptor 4 (TLR4) and inflammatory cytokines and chemokines by cultured normal melanocytes derived from lightly and darkly pigmented skin was investigated after cell stimulation with lipopolysaccharide (LPS). The basal TLR4 mRNA level in heavily pigmented cells was higher as compared to their lightly pigmented counterparts. Melanocyte exposure to LPS upregulated the expression of TLR4 mRNA and enhanced the DNA-binding activity of NF-κB p50 and p65. We found substantial differences in the LPS-stimulated expression of numerous genes encoding inflammatory cytokines and chemokines between the cells with various melanin contents. In lightly pigmented melanocytes, the most significantly upregulated genes were nicotinamide phosphoribosyltransferase (NAMPT/visfatin), the chemokines CCL2 and CCL20, and IL6, while the genes for CXCL12, IL-16 and the chemokine receptor CCR4 were the most significantly upregulated in heavily pigmented cells. Moreover, the lightly pigmented melanocytes secreted much more NAMPT, CCL2 and IL-6. The results of our study suggest modulatory effect of melanogenesis on the immune properties of normal epidermal melanocytes.
越来越多的证据表明，人类表皮黑素细胞在皮肤免疫系统中起着重要作用；然而，其色素沉着在免疫和炎症反应中的作用还未得到充分研究。在这项研究中，研究人员在细胞受到脂多糖（LPS）刺激后，研究了来自浅色和深色皮肤的培养正常黑素细胞中 Toll 样受体 4（TLR4）和炎症细胞因子和趋化因子的表达。与浅色色素沉着细胞相比，重度色素沉着细胞中 TLR4 mRNA 的基础表达水平更高。黑素细胞暴露于 LPS 会上调 TLR4 mRNA 的表达，并增强 NF-κB p50 和 p65 的 DNA 结合活性。我们发现，具有不同黑色素含量的细胞中，许多编码炎症细胞因子和趋化因子的基因在 LPS 刺激下的表达存在显著差异。在浅色色素沉着的黑素细胞中，上调最显著的基因是烟酰胺磷酸核糖基转移酶（NAMPT/visfatin）、趋化因子 CCL2 和 CCL20 以及 IL6，而在重度色素沉着的黑素细胞中，上调最显著的基因是 CXCL12、IL-16 和趋化因子受体 CCR4。此外，浅色色素沉着的黑素细胞分泌了更多的 NAMPT、CCL2 和 IL-6。我们的研究结果表明，黑素生成对正常表皮黑素细胞的免疫特性具有调节作用。
