Inflammatory mediators induced by intratracheal instillation of ultrafine amorphous silica particles.
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.
Cho
Wan-Seob
WS
Division of Toxicological Research, National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul, Republic of Korea.
Choi
Mina
M
Han
Beom Seok
BS
Cho
Minjung
M
Oh
Jaeho
J
Park
Kidae
K
Kim
Sung Jun
SJ
Kim
Seung Hee
SH
Jeong
Jayoung
J
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
D016207:Cytokines; D018836:Inflammation Mediators; D011506:Proteins; D012333:RNA, Messenger; D012822:Silicon Dioxide