Nanosized titanium dioxide enhanced inflammatory responses in the septic brain of mouse.
Nanosized titanium dioxide (TiO(2)) is used widely in various everyday products and can be applied to the medical field for diagnostic or therapeutic tools. However, its neurobiological responses have not been defined completely in the brain. To evaluate the acute inflammatory response to TiO(2) particles of two different sizes in normal and septic brains, male C57BL/6 mice were given intraperitoneal injections of fine (<1 microm) or ultrafine (21 nm) TiO(2), 30 min after vehicle or lipopolysaccaride (LPS). In the normal brain, neither fine nor ultrafine TiO(2) induced inflammation. However, in the brains of LPS-exposed mice, ultrafine TiO(2) significantly elevated proinflammatory cytokine interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNAs, and IL-1beta protein levels. Also ultrafine TiO(2) increased the levels of reactive oxygen species and activated microglia 24 h after LPS challenge. In BV2 microglial cells stimulated with LPS, ultrafine TiO(2) enhanced TNF-alpha production and augmented nuclear factor-kB binding activity. These findings suggest that nanosized TiO(2) promotes an exaggerated neuroinflammatory responses by enhancing microglial activation in the pre-inflamed brain, in part.
Shin
J A
JA
Department of Pharmacology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Lee
E J
EJ
Seo
S M
SM
Kim
H S
HS
Kang
J L
JL
Park
E M
EM
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000633:toxicity*; D001921:Brain / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001672:Biocompatible Materials; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D004247:DNA; D014025:Titanium