4 years ago

The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes

The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes
Yu-Pei Liao, André E. Nel, Chong Hyun Chang, Tian Xia, Donatello Telesca, Xiang Wang
Genetic variation constitutes an important variable impacting the susceptibility to inhalable toxic substances and air pollutants, as reflected by epidemiological studies in humans and differences among animal strains. While multiwalled carbon nanotubes (MWCNTs) are capable of causing lung fibrosis in rodents, it is unclear to what extent the genetic variation in different mouse strains influence the outcome. Four inbred mouse strains, including C57Bl/6, Balb/c, NOD/ShiLtJ, and A/J, to test the pro-fibrogenic effects of a library of MWCNTs in vitro and in vivo are chosen. Ex vivo analysis of IL-1β production in bone marrow-derived macrophages (BMDMs) as molecular initiating event (MIE) is performed. The order of cytokine production (Balb/c > A/J > C57Bl/6 > NOD/ShiLtJ) in BMDMs is also duplicated during assessment of IL-1β production in the bronchoalveolar lavage fluid of the same mouse strains 40 h after oropharyngeal instillation of a representative MWCNT. Animal test after 21 d also confirms a similar hierarchy in TGF-β1 production and collagen deposition in the lung. Statistical analysis confirms a correlation between IL-1β production in BMDM and the lung fibrosis. All considered, these data demonstrate that genetic background indeed plays a major role in determining the pro-fibrogenic response to MWCNTs in the lung. The pro-fibrogenic effects of multiwalled carbon nanotubes (MWCNTs) in bone marrow-derived macrophages (BMDM) and in the lung are tested by using four mouse strains. It is found that genetic heterogeneity impacts the pro-fibrogenic potential of MWCNTs. The ranking of MWCNT-induced IL-1β production in BMDMs correlates well with the lung fibrosis potential in different strains.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/smll.201700776

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