title: 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.
authors.affiliation: Division of Inflammation Research .
authors.forename: Koumei
authors.initials: K
authors.lastname: Shirasuna
authors.forename: Fumitake
authors.initials: F
authors.lastname: Usui
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Karasawa
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Mizukami
authors.forename: Akihide
authors.initials: A
authors.lastname: Ohkuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishimura
authors.forename: Junji
authors.initials: J
authors.lastname: Sagara
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Noda
authors.forename: Keiya
authors.initials: K
authors.lastname: Ozawa
authors.forename: Shun'ichiro
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology; D053582:Interleukin-1alpha / Q000276:immunology; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide / Q000737:chemistry / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins; C556062:IL10 protein, mouse; D058847:Inflammasomes; D053582:Interleukin-1alpha; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C498534:Pycard protein, mouse; D017382:Reactive Oxygen Species; D016753:Interleukin-10; D012822:Silicon Dioxide
keywords: Cytokines; inflammasomes; interleukin; reactive oxygen species