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根皮素通过阻断TNF-α诱导的HaCaT人角质形成细胞中的NF-κB信号通路来改善趋化因子和细胞间黏附分子-1的表达。

Phloretin ameliorates chemokines and ICAM-1 expression via blocking of the NF-κB pathway in the TNF-α-induced HaCaT human keratinocytes.

作者信息

Huang Wen-Chung, Dai Yi-Wen, Peng Hui-Ling, Kang Chiao-Wei, Kuo Chun-Yu, Liou Chian-Jiun

机构信息

Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan.

Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kwei-Shan, Tao-Yuan, Taiwan; Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, 261 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan.

出版信息

Int Immunopharmacol. 2015 Jul;27(1):32-7. doi: 10.1016/j.intimp.2015.04.024. Epub 2015 Apr 27.

DOI:10.1016/j.intimp.2015.04.024
PMID:25929446
Abstract

Previous studies found that phloretin had anti-oxidant, anti-inflammatory, and anti-tumor properties. In this study, we investigated whether phloretin could suppress the production of the intercellular adhesion molecule (ICAM)-1 and chemokines through downregulation of the nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in TNF-α-stimulated HaCaT human keratinocytes. HaCaT cells were treated with phloretin and then the cells were stimulated by TNF-α. Phloretin treatment decreased the production of IL-6, IL-8, CCL5, MDC, and TARC. Phloretin decreased ICAM-1 protein and mRNA expression, and also suppressed the adhesion of monocyte THP-1 cells to inflammatory HaCaT cells. Phloretin inhibited NF-κB translocation into the nucleus and also suppressed the phosphorylation of Akt and MAPK signal. In addition, phloretin increased heme oxygenase-1 production in a concentration-dependent manner. These results demonstrated that phloretin has anti-inflammatory effects to inhibit chemokines and ICAM-1 expressions through suppression of the NF-κB and MAPK pathways in human keratinocytes.

摘要

先前的研究发现,根皮素具有抗氧化、抗炎和抗肿瘤特性。在本研究中,我们调查了根皮素是否能通过下调核转录因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路,抑制细胞间黏附分子(ICAM)-1和趋化因子的产生,该实验以肿瘤坏死因子-α(TNF-α)刺激的HaCaT人角质形成细胞为研究对象。用根皮素处理HaCaT细胞,然后用TNF-α刺激这些细胞。根皮素处理降低了白细胞介素(IL)-6、IL-8、CCL5、巨噬细胞衍生趋化因子(MDC)和胸腺活化调节趋化因子(TARC)的产生。根皮素降低了ICAM-1蛋白和mRNA表达,还抑制了单核细胞THP-1细胞与炎性HaCaT细胞的黏附。根皮素抑制NF-κB向细胞核的转位,还抑制Akt和MAPK信号的磷酸化。此外,根皮素以浓度依赖的方式增加了血红素加氧酶-1的产生。这些结果表明,根皮素具有抗炎作用,可通过抑制人角质形成细胞中的NF-κB和MAPK途径来抑制趋化因子和ICAM-1的表达。

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