Manganese superoxide dismutase (SOD‐2), an important primary antioxidant enzyme located in mitochondria, plays a critical role in tumor progression. Reportedly, the proinflammatory cytokine, tumor necrosis factor (TNF)‐α, can increase SOD‐2 expression in a human lung adenocarcinoma cell line in vitro, indicating that TNF‐α‐mediated inflammation may regulate SOD‐2 expression, which may be related to cancer promotion. Using a urethane‐induced inflammation‐driven lung adenocarcinoma (IDLA) mice model, we investigated whether and how TNF‐α‐mediated inflammation upregulated SOD‐2 expression in lung adenocarcinoma. Our results showed that SOD‐2 was mostly expressed on surfactant protein‐C⁺ AT‐II cells (alveolar type II cell) and tumor cells in IDLA mice, which were surrounded by CD68⁺ macrophages. Blocking TNF‐α‐dependent inflammation downregulated SOD‐2 expression in inflamed lung tissues at the protumor stage and also inhibited SOD‐2 expression in tumor cells in the IDLA model. In human lung adenocarcinoma, both the number of infiltrating CD68⁺ macrophages and TNF‐α expression correlated positively with SOD‐2 expression, which is related to lymph node metastasis and TNM stage. We collected the conditioned medium from lipopolysaccharide‐activated phorbol myristate acetate‐induced THP1 (M1) cells to stimulate A549 and H1299 cells and observed that THP1‐M1 upregulated SOD‐2 by secreting TNF‐α. Blocking SOD‐2 expression significantly inhibited TNF‐α‐induced cell proliferation in A549 and H1299 cells in vitro. Thus, TNF‐α‐mediated lung inflammation can upregulate SOD‐2 expression in lung adenocarcinoma, and macrophages contribute to SOD‐2 upregulation by secreting TNF‐α.

中文翻译：

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依赖于TNF-α的肺部炎症上调超氧化物歧化酶2以促进肺腺癌中肿瘤细胞的增殖。

锰超氧化物歧化酶（SOD-2）是线粒体中一种重要的主要抗氧化酶，在肿瘤进展中起着至关重要的作用。据报道，促炎细胞因子肿瘤坏死因子（TNF）-α可以在体外增加人肺腺癌细胞系中SOD-2的表达，这表明TNF-α介导的炎症可能会调节SOD-2的表达，这可能与促进癌症。我们使用尿烷诱导的炎症驱动的肺腺癌（IDLA）小鼠模型，研究了TNF-α介导的炎症是否以及如何上调了肺腺癌中SOD-2的表达。我们的结果表明，SOD-2主要在IDLA小鼠的表面活性剂蛋白C ⁺ AT-II细胞（II型肺泡细胞）和肿瘤细胞上表达，并被CD68 ⁺包围。巨噬细胞。在IDLA模型中，阻断TNF-α依赖性炎症可下调炎症阶段肺组织中SOD-2的表达，并抑制肿瘤细胞中SOD-2的表达。在人肺腺癌中，两者的浸润CD68 ⁺巨噬细胞和TNF-α的表达与SOD-2的表达呈正相关，这与淋巴结转移和TNM分期有关。我们从脂多糖活化的佛波醇肉豆蔻酸酯乙酸盐诱导的THP1（M1）细胞中收集条件培养基以刺激A549和H1299细胞，并观察到THP1-M1通过分泌TNF-α上调了SOD-2。在体外，阻断SOD-2表达可显着抑制TNF-α诱导的A549和H1299细胞增殖。因此，TNF-α介导的肺部炎症可以上调肺腺癌中SOD-2的表达，而巨噬细胞通过分泌TNF-α来促进SOD-2的上调。