ASBESTOS INDUCES NUCLEAR FACTOR KAPPA-B (NF-KAPPA-B) DNA-BINDING ACTIVITY AND NF-KAPPA-B-DEPENDENT GENE-EXPRESSION IN TRACHEAL EPITHELIAL-CELLS
ASBESTOS INDUCES NUCLEAR FACTOR KAPPA-B (NF-KAPPA-B) DNA-BINDING ACTIVITY AND NF-KAPPA-B-DEPENDENT GENE-EXPRESSION IN TRACHEAL EPITHELIAL-CELLS
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DOI：
10.1073/pnas.92.18.8458
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发表时间：
1995-08-29
影响因子：
11.1
通讯作者：
MOSSMAN, BT
中科院分区：
文献类型：
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作者：
JANSSEN, YMW;BARCHOWSKY, A;MOSSMAN, BT
核因子-κ B（NF-κ B）是一种转录因子，调节石棉相关疾病的炎症和细胞增殖的内在基因表达。在这里的研究中，青石棉引起仓鼠气管上皮（HTE）细胞中与核NF-κ B结合DNA元件结合的蛋白质的长期和剂量反应性增加。这种结合受细胞谷胱甘肽水平的调节。识别NF-κ B家族的p65和p50蛋白质成员的抗体揭示了两种DNA复合物中的这些蛋白质。用含有与荧光素酶报告基因连接的六个NF-κ B结合DNA共有位点的构建体进行的瞬时转染试验表明，石棉诱导NF-κ B依赖性基因的转录激活，这一观察结果通过对HTE细胞中c-myc mRNA水平的北方印迹分析得到证实，研究表明，NF-κ B B诱导石棉是一个关键事件，在石棉相关肺癌的发病机制中涉及的多个基因的调节。
Nuclear factor kappa B (NF-kappa B) is a transcription factor regulating expression of genes intrinsic to inflammation and cell proliferation-features of asbestos-associated diseases. In studies here, crocidolite asbestos caused protracted and dose-responsive increases in proteins binding to nuclear NF-kappa B-binding DNA elements in hamster tracheal epithelial (HTE) cells. This binding was modulated by cellular glutathione levels. Antibodies recognizing p65 and p50 protein members of the NF-kappa B family revealed these proteins in two of the DNA complexes. Transient transfection assays with a construct containing six NF-kappa B-binding DNA consensus sites linked to a luciferase reporter gene indicated that asbestos induced transcriptional activation of NF-kappa B-dependent genes, an observation that was confirmed by Northern blot analyses for c-myc mRNA levels in HTE cells, Studies suggest that NF-kappa B induction by asbestos is a key event in regulation of multiple genes involved in the pathogenesis of asbestos-related lung cancers.