Cancer Immunology Program, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria, Australia.
Immunol Cell Biol. 2012 Nov;90(10):983-6. doi: 10.1038/icb.2012.46. Epub 2012 Sep 25.
Asbestos exposure can result in serious and frequently lethal diseases, including malignant mesothelioma. The host sensor for asbestos-induced inflammation is the NLRP3 inflammasome and it is widely assumed that this complex is essential for asbestos-induced cancers. Here, we report that acute interleukin-1β production and recruitment of immune cells into peritoneal cavity were significantly decreased in the NLRP3-deficient mice after the administration of asbestos. However, NLRP3-deficient mice displayed a similar incidence of malignant mesothelioma and survival times as wild-type mice. Thus, early inflammatory reactions triggered by asbestos are NLRP3-dependent, but NLRP3 is not critical in the chronic development of asbestos-induced mesothelioma. Notably, in a two-stage carcinogenesis-induced papilloma model, NLRP3-deficient mice showed a resistance phenotype in two different strain backgrounds, suggesting a tumour-promoting role of NLRP3 in certain chemically-induced cancer types.
石棉暴露可导致严重且常致命的疾病，包括恶性间皮瘤。石棉诱导炎症的宿主传感器是 NLRP3 炎性小体，人们普遍认为该复合物对于石棉诱导的癌症是必需的。在这里，我们报告在给予石棉后，NLRP3 缺陷型小鼠的急性白细胞介素-1β产生和免疫细胞向腹腔的募集明显减少。然而，NLRP3 缺陷型小鼠的恶性间皮瘤发生率和野生型小鼠的存活时间相似。因此，石棉引发的早期炎症反应依赖于 NLRP3，但 NLRP3 在石棉诱导的间皮瘤的慢性发展中并不关键。值得注意的是，在两阶段致癌作用诱导的乳头瘤模型中，NLRP3 缺陷型小鼠在两种不同的遗传背景下表现出抗性表型，表明 NLRP3 在某些化学诱导的癌症类型中具有促进肿瘤的作用。
