Low-dose gamma-irradiation inhibits IL-6 secretion from human lung fibroblasts that promotes bronchial epithelial cell transformation by cigarette-smoke carcinogen
Low-dose gamma-irradiation inhibits IL-6 secretion from human lung fibroblasts that promotes bronchial epithelial cell transformation by cigarette-smoke carcinogen
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DOI：
10.1093/carcin/bgs159
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发表时间：
2012-07-01
期刊：
影响因子：
4.7
通讯作者：
Lin, Yong
中科院分区：
文献类型：
--
作者：
Chen, Wenshu;Xu, Xiuling;Lin, Yong
尽管数十年来研究定义低剂量（< 100 mGy）电离光子辐射（LDR）对健康的影响，但LDR与人类癌症风险之间的关系仍然难以捉摸。由于化学致癌物改变了肿瘤微环境，这对癌症的发展至关重要，我们研究了LDR在调节基质细胞对化学致癌物诱导的肺癌发展的反应中的作用和机制。烟雾致癌物苯并[a]芘二醇环氧化合物（BPDE）诱导人肺成纤维细胞分泌促炎细胞因子如白细胞介素-6（IL-6）、CXCL 1和CXCL 5，单剂量LDR可抑制BPDE的分泌。NF-B的激活，这是重要的BPDE诱导的IL-6分泌，也有效地抑制LDR。此外，从BPDE处理的成纤维细胞的条件培养基激活STAT 3在永生化的正常人支气管上皮细胞系Beas-2B，这是封闭的IL-6中和抗体。来自LDR引发的和BPDE处理的成纤维细胞的条件培养基显示激活STAT 3的能力降低。此外，IL-6在体外增强BPDE诱导的Beas-2B细胞转化。这些结果表明，LDR抑制香烟烟雾诱导的肺癌发生通过抑制细胞因子的分泌，如IL-6从肺肿瘤易感微环境中的成纤维细胞。
Despite decades of research in defining the health effects of low-dose (< 100 mGy) ionizing photon radiation (LDR), the relationship between LDR and human cancer risk remains elusive. Because chemical carcinogens modify the tumor microenvironment, which is critical for cancer development, we investigated the role and mechanism of LDR in modulating the response of stromal cells to chemical carcinogeninduced lung cancer development. Secretion of proinflammatory cytokines such as interleukin-6 (IL-6), CXCL1 and CXCL5 from human lung fibroblasts was induced by cigarette-smoke carcinogen benzo[a]pyrene diol epoxide (BPDE), which was inhibited by a single dose of LDR. The activation of NF-B, which is important for BPDE-induced IL-6 secretion, was also effectively suppressed by LDR. In addition, conditioned media from BPDE-treated fibroblasts activated STAT3 in the immortalized normal human bronchial epithelial cell line Beas-2B, which was blocked with an IL-6 neutralizing antibody. Conditioned medium from LDR-primed and BPDE-treated fibroblast showed diminished capacity in activating STAT3. Furthermore, IL-6 enhanced BPDE-induced Beas-2B cell transformation in vitro. These results suggest that LDR inhibits cigarette smokeinduced lung carcinogenesis by suppressing secretion of cytokines such as IL-6 from fibroblasts in lung tumor-prone microenvironment.