Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression.
Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression.
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DOI：
10.1038/jid.2009.384
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发表时间：
2010-04
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各种皮脂游离脂肪酸（FFA）已经显示出对广泛的革兰氏阳性菌的抗菌活性，从而表明它们至少部分地对皮肤表面的直接抗微生物活性负责。在这项研究中，我们研究了皮脂游离脂肪酸对抗菌肽（AMP）介导的人类皮脂细胞先天免疫防御的影响。将月桂酸、棕榈酸或油酸（OA）与人皮脂腺细胞孵育，显著增强其人β-防御素（hBD）-2（在皮肤中发现的主要AMP之一）的表达，而未观察到hBD-1、hBD-3和人cathelicidin LL-37的显著增加。分泌的hBD-2可通过蛋白质印迹法在与每种FFA孵育的皮脂细胞培养物的上清液中检测到，但不与载体对照孵育。FFA孵育的皮脂腺细胞培养物的上清液显示出对痤疮丙酸杆菌的抗微生物活性，而人皮脂腺细胞的增强的抗微生物活性被抗hBD-2 IgG中和。此外，通过用抗人CD 36 IgG阻断皮脂细胞表面的分化簇（CD）36脂肪酸移位酶或用BMS-345541（一种抑制性κB激酶的高选择性抑制剂）阻断NF-κB信号通路，抑制FFA诱导的hBD-2表达。这些数据表明，皮脂游离脂肪酸上调人皮脂细胞中hBD-2的表达，这可能增强人皮脂腺的消毒活性。FFA诱导的hBD-2上调通过CD 36介导的FFA摄取和NF-κ B介导的反式激活来促进。小鼠β-防御素4（hBD-2的小鼠直系同源物）的上调也在表皮应用OA（测试的最hBD-2诱导的FFA）后在小鼠耳皮肤的毛囊皮脂腺中观察到。本报告强调了使用FFAs作为多功能抗微生物治疗剂用于寻常痤疮治疗的潜力; FFAs可以提供针对痤疮丙酸杆菌的直接抗菌活性，并通过诱导hBD-2在皮脂腺细胞中的表达来增强皮肤的先天性抗菌防御。
Various sebum free fatty acids (FFAs) have shown antibacterial activity against a broad range of Gram-positive bacteria, resulting in the suggestion that they are accountable, at least partially, for the direct antimicrobial activity of the skin surface. In this study, we examined the effects of sebum FFAs on the antimicrobial peptide (AMP)-mediated innate immune defense of human sebocytes. Incubation of lauric acid, palmitic acid, or oleic acid (OA) with human sebocytes dramatically enhanced their expression of human β-defensin (hBD)-2, one of the predominant AMPs found in the skin, whereas remarkable increases in hBD-1, hBD-3, and human cathelicidin LL-37 were not observed. Secreted hBD-2 was detectable by western blotting in the supernatant of sebocyte culture incubated with each FFA, but not with a vehicle control. The supernatant of FFA-incubated sebocyte culture showed antimicrobial activity against Propionibacterium acnes, whereas the enhanced antimicrobial activity of human sebocytes was neutralized by anti-hBD-2 IgG. In addition, the FFA-induced hBD-2 expression was suppressed by blocking the cluster of differentiation (CD)36 fatty acid translocase on the surface of sebocytes with anti-human CD36 IgG or blocking the NF-κB signaling pathway with BMS-345541, a highly selective inhibitor of inhibitory κB kinase. These data suggest that sebum FFAs upregulate the expression of hBD-2 in human sebocytes, which may enhance the disinfecting activity of the human sebaceous gland. The FFA-induced upregulation of hBD-2 is facilitated by CD36-mediated FFA uptake and NF-κB-mediated transactivation. The upregulation of mouse β-defensin 4, a mouse ortholog for hBD-2, was also observed in the hair follicle sebaceous glands of mouse ear skin after an epicutaneous application of OA, the most hBD-2-inducible FFA tested. This report highlights the potential of using FFAs as a multifunctional antimicrobial therapy agent for acne vulgaris treatment; FFAs may provide direct antibacterial activities against P. acnes and enhance the skin’s innate antibacterial defense by inducing the expression of hBD-2 in sebocytes as well.
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影响因子：
3
作者：
Fujie, T;Shikiji, T;Arase, S
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