Nanosilica-induced placental inflammation and pregnancy complications: Different roles of the inflammasome components NLRP3 and ASC

Abstract

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.

• Cytokines
• inflammasomes
• interleukin
• reactive oxygen species

Acknowledgements

We are grateful to Masako Sakurai, Yumi Ohde and Sumiyo Watanabe for their technical assistance, Dr. Vishva M. Dixit (Genentech) for providing the Nlrp3^–/– mice.

Declaration of interest

This study received grants from the Japan Society for the Promotion of Science (JSPS) through the “Funding Program for Next Generation World-Leading Researchers (NEXT Program),” initiated by the Council for Science and Technology Policy (CSTP) (MT), MEXT-supported program for the Strategic Foundation at Private Universities (MT), Grant-in-Aid for Young Scientists (B) (KS), Kanzawa Medical Research Foundation (KS) and Jichi Medical University Young Investigator Award (KS). The authors report no conflicts of interest.

Supplementary material available online

Supplemental Figures S1–S4