Cadmium induces lung inflammation independent of lung cell proliferation: a molecular approach.
Cadmium induces lung inflammation independent of lung cell proliferation: a molecular approach.
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DOI：
10.1186/1476-9255-6-19
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发表时间：
2009-06-12
期刊：
影响因子：
--
通讯作者：
Bhattacharyya A
中科院分区：
文献类型：
--
作者：
Kundu S;Sengupta S;Chatterjee S;Mitra S;Bhattacharyya A
镉是一种与炎症相关的外源性物质，被认为是一种强致癌物质。慢性感染引起的炎症和细胞增殖之间的关系已被研究，但其机制尚不完全清楚。虽然镉的毒性模式在动物细胞中得到了很好的表征，但仍需要进一步的研究。以前我们报道过镉诱导瑞士白化病小鼠的免疫细胞死亡。在本研究中，我们发现，而不是诱导细胞死亡机制，镉在低浓度触发小鼠肺细胞增殖，我们的结果表明，在诱导增殖之前，它会导致严重的炎症。用不同浓度的镉处理瑞士白化病小鼠，以测定LD 50。根据暴露时间（15、30、45、60天）将小鼠细分（各5只小鼠），每周一次给予亚致死剂量（5 mg/Kg体重）的氯化镉和布洛芬（50 mg/Kg体重，推荐剂量）。进行SEM和组织学检查作为细胞形态变化的证据。通过考克斯-2和MMPs的表达来测量炎症。采用Western blot、ELISA和免疫沉淀法检测促炎细胞因子（考克斯-2、IL-6）、信号转导和细胞周期调控分子（STAT 3、Akt、CyclinD1）的表达。用彗星试验证明其致突变性。通过细胞计数、细胞周期和DNA分析来测定细胞增殖。低浓度镉长期暴露可导致促炎细胞因子和细胞周期调节分子的上调。虽然伊曲康等非甾体类抗炎药能降低炎性细胞因子的表达，但对染镉肺细胞的增殖无抑制作用。我们的研究结果证明，镉引起炎症和细胞增殖，当应用在低剂量，但增殖性变化发生独立的炎症。
Cadmium is one of the inflammation-related xenobiotics and has been regarded as a potent carcinogen. The relationship between inflammation and cell proliferation due to chronic infection has been studied, but the mechanism is not fully clear. Though the mode of cadmium toxicity is well characterized in animal cells, still it requires some further investigations. Previously we reported that cadmium induces immune cell death in Swiss albino mice. In the present study we showed that instead of inducing cell death mechanism, cadmium in low concentration triggers proliferation in mice lung cell and our results reveals that prior to the induction of proliferation it causes severe inflammation. Swiss albino mice were treated with different concentrations of cadmium to determine the LD50. Mice were subdivided (5 mice each) according to the exposure period (15, 30, 45, 60 days) and were given sub lethal dose (5 mg/Kg body weight) of cadmium chloride and ibuprofen (50 mg/Kg body weight, recommended dose) once in a week. SEM and histology were performed as evidence of changes in cellular morphology. Inflammation was measured by the expression of Cox-2 and MMPs. Expression of proinflammatory cytokines (Cox-2, IL-6), signaling and cell cycle regulatory molecules (STAT3, Akt, CyclinD1) were measured by western blot, ELISA and immunoprecipitation. Mutagenecity was evidenced by comet assay. Cell proliferation was determined by cell count, cell cycle and DNA analysis. Prolonged exposure of low concentration of cadmium resulted in up regulation of proinflammatory cytokines and cell cycle regulatory molecules. Though NSAIDs like Ibuprofen reduces the expression of inflammatory cytokines, but it did not show any inhibitory effect on cadmium adopted lung cell proliferation. Our results prove that cadmium causes both inflammation and cell proliferation when applied in a low dose but proliferative changes occur independent of inflammation.
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