Laboratory of Pathology, College of Oriental Medicine, Daejeon University, Daejeon 300-716, Republic of Korea.
J Dermatol Sci. 2012 Mar;65(3):179-88. doi: 10.1016/j.jdermsci.2011.11.005. Epub 2011 Nov 20.
Tumor necrosis factor-alpha (TNF-α) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear.
To explore the lipogenic effect by TNF-α and possible molecular mechanisms in sebocyte.
Using SZ95 human sebocytes, lipid formation by TNF-α was assessed by Oil Red O, Nile Red staining and thin layer chromatography (TLC). Expression of lipogenic genes and activation of mitogen-activated protein kinase as well as Akt were examined by real-time polymerase chain reaction and/or Western blot analysis. Activation of peroxisome proliferator-activated receptor (PPAR) was evaluated by luciferase assay using PPAR response element containing reporter plasmids. Involvement of c-Jun N-terminal kinase (JNK) and Akt in TNF-α-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors.
TNF-α treatment significantly increased formation of lipid droplets in accordance with up-regulated expression of FAS and activation of SREBP-1, but not PPARs. Suppression of phosphorylated JNK by the JNK inhibitor SP600125 greatly diminished TNF-α-induced expression of FAS and SREBP-1. TNF-α could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA.
TNF-α induces lipogenesis in SZ95 human sebocytes through the JNK and phosphoinositide-3-kinase/Akt pathways. These results will be valuable in developing therapeutic strategies for control of seborrhea and acne.
肿瘤坏死因子-α（TNF-α）是参与痤疮发生的重要病理生理因子。然而，其作用尚不清楚。
探讨 TNF-α在皮脂腺细胞中的致脂作用及其可能的分子机制。
采用 SZ95 人皮脂腺细胞，用油红 O、尼罗红染色和薄层层析（TLC）评估 TNF-α 的脂生成作用。通过实时聚合酶链反应和/或 Western blot 分析检测致脂基因的表达和丝裂原活化蛋白激酶（MAPK）以及 Akt 的激活。通过含有 PPAR 反应元件的报告质粒的荧光素酶测定评估过氧化物酶体增殖物激活受体（PPAR）的激活。通过特定的小分子干扰 RNA 和抑制剂研究 JNK 和 Akt 在 TNF-α诱导的脂生成中的作用。
TNF-α 处理显著增加了脂滴的形成，伴随着 FAS 和 SREBP-1 的表达上调，但 PPARs 没有上调。JNK 抑制剂 SP600125 抑制磷酸化 JNK 可显著减少 TNF-α诱导的 FAS 和 SREBP-1 的表达。用 siRNA 减弱 Akt 表达时，TNF-α不能诱导脂生成蛋白的表达和脂质合成。
TNF-α 通过 JNK 和磷酯酰肌醇-3-激酶/Akt 途径诱导 SZ95 人皮脂腺细胞的脂生成。这些结果对于开发控制皮脂溢和痤疮的治疗策略将具有重要价值。
