Shirasuna Koumei, Usui Fumitake, Karasawa Tadayoshi, Kimura Hiroaki, Kawashima Akira, Mizukami Hiroaki, Ohkuchi Akihide, Nishimura Satoshi, Sagara Junji, Noda Tetsuo, Ozawa Keiya, Taniguchi Shun'ichiro, Takahashi Masafumi
Division of Inflammation Research .
Nanotoxicology. 2015;9(5):554-67. doi: 10.3109/17435390.2014.956156. Epub 2014 Sep 11.
Despite the increasing commercial use of nanoparticles, little is known about their effects on placental inflammation and pregnancy complications. In this study, nanosilica (NS) particles upregulated the inflammasome component nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) and induced placental inflammation and reactive oxygen species (ROS) generation, resulting in pregnancy complications. Furthermore, NS-induced pregnancy complications were markedly improved in Nlrp3(-/-) mice but not in component apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)-deficient (Asc(-/-)) mice, indicating the independence of NLRP3 inflammasomes. Pregnancy complications in Nlrp3(-/-) and Asc(-/-) mice phenotypes were dependent on the balance between interleukin (IL)-1α and IL-10. NS-induced pregnancy complications were completely prevented by either inhibition of ROS generation or forced expression of IL-10. Our findings provide important information about NS-induced placental inflammation and pregnancy complications and the novel pathophysiological roles of NLRP3 and ASC in pregnancy.
尽管纳米颗粒的商业用途日益增加，但人们对其对胎盘炎症和妊娠并发症的影响知之甚少。在本研究中，纳米二氧化硅（NS）颗粒上调了炎性小体成分核苷酸结合寡聚化结构域样受体（NLR）家族含pyrin结构域3（NLRP3），并诱导胎盘炎症和活性氧（ROS）生成，导致妊娠并发症。此外，NS诱导的妊娠并发症在Nlrp3基因敲除（Nlrp3(-/-)）小鼠中显著改善，但在含半胱天冬酶募集结构域的凋亡相关斑点样蛋白（ASC）缺陷（Asc(-/-)）小鼠中未改善，表明NLRP3炎性小体具有独立性。Nlrp3(-/-)和Asc(-/-)小鼠表型中的妊娠并发症取决于白细胞介素（IL）-1α和IL-10之间的平衡。通过抑制ROS生成或强制表达IL-10可完全预防NS诱导的妊娠并发症。我们的研究结果提供了有关NS诱导的胎盘炎症和妊娠并发症以及NLRP3和ASC在妊娠中的新病理生理作用的重要信息。
