Altered NF-κB gene expression and collagen formation induced by polyunsaturated fatty acids
Altered NF-κB gene expression and collagen formation induced by polyunsaturated fatty acids
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DOI：
10.1016/j.jnutbio.2005.01.016
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发表时间：
2005-08-01
影响因子：
5.6
通讯作者：
Turek, JJ
中科院分区：
文献类型：
--
作者：
Jia, Y;Turek, JJ
无法控制重要器官中的胶原蛋白形成（例如，纤维化）或刺激结缔组织中健康的胶原蛋白产生（CP）（例如，韧带）是死亡和残疾的主要原因。本研究验证了花生四烯酸（AA）和二十碳五烯酸（EPA）通过改变核因子-κ B（NF-κ B）通路中的基因表达来影响3 T3-Swiss成纤维细胞中CP的假设。3 T3-Swiss成纤维细胞在含有AA或EPA的培养基中生长。脂多糖（LPS）激活NF-κ B，孤雌激素阻断，EPA处理的细胞在暴露于LPS时NF-κ B通路中的基因表达增加，并产生更多的胶原。在EPA处理的细胞中，小白菊在更大程度上阻断NF-κ B活化，并且还降低NF-κ B活化诱导的CP。在EPA处理的细胞中表达增加的NF-κ B信号通路中的基因包括toll样受体4（Tlr 4）、衔接蛋白[TNF受体相关因子6（Traf 6）、髓样分化初级应答基因88]、信号转导激酶（NF-κ B诱导激酶，κ轻链多肽基因增强子亚型的抑制剂），抑制蛋白（I-κ B α链），转录因子（κ轻链基因增强子核因子，p105和NF-κ B亚单位p100），DNA结合蛋白（cAMP应答元件结合蛋白）和已知影响CP的应答基因[白细胞介素6（IL-6），诱导型一氧化氮合酶（iNOS），单核细胞趋化蛋白-1]。这项研究提出了脂肪酸可以作为佐剂与其他疗法联合使用的可能性（例如，选择性靶向NF-κ B途径）以控制胶原蛋白形成。(c)2005年爱思唯尔公司All rights reserved.
Inability to control collagen formation in vital organs (e.g., fibrosis) or stimulate healthy collagen production (CP) in connective tissues (e.g., ligaments) is a major cause of death and disability. This study tested the hypothesis that arachidonic acid (AA) and eicosapentaenoic acid (EPA) influenced CP in 3T3-Swiss fibroblasts by altering gene expression in the nuclear factor-kappa B (NF-kappa B) pathway. 3T3-Swiss fibroblasts were grown in medium containing either AA or EPA. Lipopolysaccharide (LPS) was used to activate NF-kappa B, and parthenolide was used to block it. Cells treated with EPA had increased expression of genes in the NF-kappa B pathway when exposed to LPS and also produced more collagen. Parthenolide blocked NF-kappa B activation to a greater extent in EPA-treated cells and also decreased CP induced by NF-kappa B activation. Genes in the NF-kappa B signaling pathway that had increased expression in EPA-treated cells included the toll-like receptor 4 (Tlr4), adaptor proteins [TNF receptor-associated factor 6 (Traf6), myeloid differentiation primary response gene 88], signal transduction kinases (NF-kappa B-inducing kinase, inhibitors of kappa light polypeptide gene enhancer isoforms), inhibitor protein (I-kappa B alpha chain), transcription factors (nuclear factor of kappa light chain gene enhancer, p105 and NF-kappa B subunit p100), DNA binding proteins (cAMP response element binding protein) and response genes known to affect CP [interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), monocyte chemotactic protein-1]. This study raises the possibility that fatty acids may be used as adjuvants in combination with other therapies (e.g., selective targeting of the NF-kappa B pathway) to control collagen formation. (c) 2005 Elsevier Inc. All rights reserved.