Department of Zoology, University of Calcutta, 35, Ballygange Circular Road, Kolkta-700019, India.
J Inflamm (Lond). 2009 Jun 12;6:19. doi: 10.1186/1476-9255-6-19.
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.
镉是一种与炎症相关的异生物质，已被认为是一种强有力的致癌物质。慢性感染引起的炎症和细胞增殖之间的关系已经被研究过，但机制尚不完全清楚。尽管镉在动物细胞中的毒性模式已经得到很好的描述，但仍需要进一步研究。我们之前报道过，镉会导致瑞士白化小鼠的免疫细胞死亡。在本研究中，我们表明，在低浓度下，镉不会引发细胞死亡机制，而是会触发小鼠肺部细胞的增殖，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小鼠，以确定半数致死量。根据暴露时间（15、30、45、60 天）将小鼠分为（每组 5 只），并给予亚致死剂量（5mg/Kg 体重）的氯化镉和布洛芬（50mg/Kg 体重，推荐剂量）每周一次。扫描电子显微镜和组织学用于证明细胞形态变化的证据。通过 Cox-2 和 MMPs 的表达来测量炎症。通过 Western blot、ELISA 和免疫沉淀测量促炎细胞因子（Cox-2、IL-6）、信号和细胞周期调节分子（STAT3、Akt、CyclinD1）的表达。彗星试验证明致突变性。通过细胞计数、细胞周期和 DNA 分析来确定细胞增殖。
长时间暴露于低浓度的镉会导致促炎细胞因子和细胞周期调节分子的上调。尽管非甾体抗炎药（如布洛芬）可以降低炎症细胞因子的表达，但它对镉诱导的肺部细胞增殖没有显示出任何抑制作用。
我们的结果证明，当以低剂量应用时，镉会引起炎症和细胞增殖，但增殖变化发生在炎症之外。
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