NF-κB p65 and p105 implicate in interleukin 1β-mediated COX-2 expression in melanoma cells
NF-κB p65 and p105 implicate in interleukin 1β-mediated COX-2 expression in melanoma cells
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DOI：
10.1371/journal.pone.0208955
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发表时间：
2018-12-18
期刊：
影响因子：
3.7
通讯作者：
Sugiya, Hiroshi
中科院分区：
文献类型：
--
作者：
Kitanaka, Nanako;Nakano, Rei;Sugiya, Hiroshi
癌细胞产生的炎症和微环境因子被认为直接或间接地促进癌细胞的生长。前列腺素，包括前列腺素E2，在影响肿瘤发展的微环境因素中起关键作用，并由限速酶环氧合酶2(COX-2)产生。在这项研究中，我们使用促炎症细胞因子IL-1β(IL-1β)处理的犬黑色素瘤细胞，研究了转录因子核因子-kappa B(NF-kappa B)在IL-1β诱导的COX-2表达中的信号转导。IL-1β以时间和剂量依赖的方式诱导前列腺素E_2释放和COX-2mRNA表达。在NF-kappa B抑制剂BAY11-7082和TPC-1处理的细胞中，IL-1β介导的前列腺素E2的释放和COX-2mRNA的表达均受到抑制。IL-1β还可引起核因子-kappaB家族成员p65/rela和p105/nf-kappa B1的磷酸化。在两种核因子-kappa B抑制剂的存在下，IL-1β诱导的p65和p105的磷酸化都被减弱。在转导p65或p105 siRNA的黑色素瘤细胞中，IL-1β介导的COX-2mRNA表达受到抑制。这些发现表明，核因子-kappaB信号的典型激活在黑色素瘤细胞的炎症状态中起着至关重要的作用。
Inflammatory and microenvironmental factors produced by cancer cells are thought to directly or indirectly promote cancer cell growth. Prostaglandins, including prostaglandin E2, have key roles as a microenvironment factor in influencing the development of tumors, and are produced by the rate limiting enzyme cyclooxygenase 2 (COX-2). In this study, we used canine melanoma cells treated with the proinflammatory cytokine interleukin 1 beta (IL-1 beta) and investigated the transcriptional factor nuclear factor-kappa B (NF-kappa B) signaling in IL-1 beta-induced COX-2 expression. IL-1 beta induced prostaglandin E2 release and COX-2 mRNA expression in a time- and dose-dependent manner. In the cells treated with the NF-kappa B inhibitors BAY11-7082 and TPC-1, IL-1 beta-mediated prostaglandin E2 release and COX-2 mRNA expression were inhibited. IL-1 beta also provoked phosphorylation of p65/RelA and p105/NF-kappa B1, which are members of the NF-kappa B families. The IL-1 beta-induced phosphorylation of p65 and p105 was attenuated in the presence of both NF-kappa B inhibitors. In melanoma cells transfected with siRNA of p65 or p105, IL-1 beta-mediated COX-2 mRNA expression was inhibited. These findings suggest that canonical activation of NF-kappa B signaling plays a crucial role for inflammatory states in melanoma cells.