Journal
TOXICOLOGY LETTERS
Volume 299, Issue -, Pages 1-10Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2018.08.019
Keywords
Diesel exhaust particle; Let-7; LIN28B; Inflammatory response; Intra-tracheal instillation
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Funding
- Key Program of National Natural Science Foundation of China [NSFC 91643203]
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Exposure to diesel exhaust particle (DEP) is closely related to inflammatory response in respiratory system. To understand the underlying molecular mechanism by which DEP induces pulmonary inflammatory response, we conducted DEP exposure experiments in vivo and in vitro. In vivo, each mouse was exposed to DEP suspension (100 pg of DEP) or vehicle only once in single infra-tracheal instillation (IT) section, or was exposed to DEP suspension (12.5 pg or 50 pg of DEP) or vehicle 12 times in repeated IT section. DEP exposure induced significant pathological injuries with substantial neutrophils infiltration and the increased level of pro-inflammatory cytokine IL-6 in mouse lungs. Consistently, elevated IL6 mRNA level was also observed in DEP treatment group (100 mu g/ml) in vitro. In addition, DEP exposure exerted the similar influence on the expression of let-7d and let7g microRNAs in vivo and in vitro. To verify the possible role of LIN28B/let-7 axis in the regulation of IL6 expression following DEP exposure, we applied RNAi technology in vitro, and found increased IL6 mRNA expression was alleviated or neutralized in DEP exposure groups after LIN28B silencing or after let-7d or let-7g over-expression. Taken together, we conclude that LIN28B/let-7 axis might be involved in inflammatory response induced by DEP exposure.
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