title: Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles.
abstract: In order to evaluate the pulmonary effects and inflammatory mechanisms of ultrafine amorphous silica particles (UFASs), the UFASs suspension was prepared in PBS and intratracheally administered to A/J mice at doses of 0, 2, 10 and 50mg/kg (n=5 per group). Animals were sacrificed at 24h, and 1, 4 or 14 weeks following exposures. At each time point, a bronchoalveolar lavage fluid analysis, histopathological examination, quantitative real-time PCR and immunohistochemistry of the lung tissues were assessed. The intratracheal instillation of UFASs significantly increased the lung weights and total BAL cells following exposures. The histopathological examination revealed that UFASs-induced severe inflammation, with neutrophils, at an early stage and chronic granulomatous inflammation at the later stage. The mRNA and protein levels of IL-1beta, IL-6, IL-8, TNF-alpha, MCP-1 and MIP-2 in lung tissues were significantly increased during the early stages, but there were no changes after weeks 1 (TNF-alpha) or 4 (IL-1beta, IL-6, IL-8, MCP-1 and MIP-2). Instillation of UFASs-induced transient, but very severe lung inflammation. Therefore, the cytokines (IL-1beta, IL-6, IL-8 and TNF-alpha) and chemokines (MCP-1 and MIP-2) play important roles in the inflammation induced by the intratracheal instillation of UFASs.
authors.affiliation: Division of Toxicological Research, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Republic of Korea.
authors.forename: Wan-Seob
authors.initials: WS
authors.lastname: Cho
authors.forename: Mina
authors.initials: M
authors.lastname: Choi
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Han
authors.forename: Minjung
authors.initials: M
authors.lastname: Cho
authors.forename: Jaeho
authors.initials: J
authors.lastname: Oh
authors.forename: Kidae
authors.initials: K
authors.lastname: Park
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Kim
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Jayoung
authors.initials: J
authors.lastname: Jeong
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010316:Particle Size; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000096:biosynthesis; D012822:Silicon Dioxide / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011506:Proteins; D012333:RNA, Messenger; D012822:Silicon Dioxide