title: A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice.
abstract: Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-γ and IL-4 reached the maximum at Day 1, and IL-5, TGF-β, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.
authors.affiliation: Environmental Health Risk Research Department, National Institute of Environmental Research, Kyungseo-dong, Seo-gu, Incheon, 404-708, Korea. pej303@korea.kr
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.forename: Jinkyu
authors.initials: J
authors.lastname: Roh
authors.forename: Soo-Nam
authors.initials: SN
authors.lastname: Kim
authors.forename: Min-Sung
authors.initials: MS
authors.lastname: Kang
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Han
authors.forename: Younghun
authors.initials: Y
authors.lastname: Kim
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Choi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D005434:Flow Cytometry; D007322:Instillation, Drug; D007442:Intubation, Intratracheal; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D000090204:Mesothelin; D051379:Mice; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology; D013499:Surface Properties
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; C000715528:Msln protein, mouse; D037742:Nanotubes, Carbon; D003094:Collagen; D000090204:Mesothelin