XXXX nanoparticles induce biphasic gene expression changes associated with inflammatory responses in the lungs of C57BL/6 @entity19 following a single intratracheal instillation.

@entity19 @entity1576 @entity17244 @entity55
UNASSIGNED: Inhalation of @entity17244 nanoparticles (CBNPs) causes @entity55 ; however, time course data to evaluate the detailed evolution of lung inflammatory responses are lacking. Here we establish a time-series of lung inflammatory response to CBNPs. Female C57BL/6 @entity19 were intratracheally instilled with 162 g CBNPs alongside vehicle controls. Lung tissues were examined 3h, and 1, 2, 3, 4, 5, 14, and 42days (d) post-exposure. Global gene expression and @entity55 were assessed. DNA damage was evaluated in bronchoalveolar lavage (BAL) cells and lung tissue using the comet assay. Increased neutrophil influx was observed at all time-points. DNA strand breaks were increased in BAL cells 3h post-exposure, and in lung tissues 2-5d post-exposure. Approximately 2600 genes were differentially expressed (  1.5 fold; p <=0.05) across all time-points in the lungs of exposed @entity19 . Altered transcript levels were associated with immune-inflammatory response and acute phase response pathways, consistent with the BAL profiles and expression changes found in common @entity1576 . Genes involved in DNA repair, apoptosis, cell cycle regulation, and muscle contraction were also differentially expressed. Gene expression changes associated with inflammatory response followed a biphasic pattern, with initial changes at 3h post-exposure declining to base-levels by 3d, increasing again at 14d, and then persisting to 42d post-exposure. Thus, this single CBNP exposure that was equivalent to nine 8-h working days at the current Danish occupational exposure limit induced biphasic inflammatory response in gene expression that lasted until 42d post-exposure, raising concern over the chronic effects of CBNP exposure.
