Dataset Information

Impact of cellular crosstalk on the cytochrome expression in an in vitro test system relevant for the alveolar barrier

ABSTRACT: Purpose: For humans, inhalation is considered as the main exposure route to chemicals, which is the reason why lung toxicity studies should be considered as a priority. Inhalation studies are often performed in vivo in rodents. Therefore, in vitro models may represent a valid and efficient alternative to predict the acute toxicity effects of inhaled chemicals on human health. The models used in this study are really simple in vitro systems either constituted by THP1 alone or THP1 cocultured with A549. This special designed has the purpose to study the impact of cellular cross talk on the THP 1 immune cells when exposed to a chemical which is BaP in the present work. Results: We describe the effects after 48 hours of exposure BaP in order to evaluate the importance of the cellular crosstalk in cell sensitivity toxicological effects of BaP. The set of parameters used to assess this cellular crosstalk included transcriptomics, cell imaging and enzymatic activity. The exposure did not cause any significant decrease of viability; all the parameters revealed the toxicity of the BaP. Regarding the global transcript, among differentially expressed genes (DEG) were found genes related to the enhancement of immune cells. Conclusion: Coculture in the used of in vitro model drastically change the gene expression profile in THP1 cells, but similar effects were observed between the monoculture and the culture exposed to BaP. However the number of altered mechanism in the THP1 cocultured cells exposed to BaP was larger supporting the importance to take into account the cell interactions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE234397 | GEO | 2023/06/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Occupational exposure to crystalline silica results in serious health effects, most notably, silicosis and cancer. A proper understanding of the mechanism(s) underlying the initiation and progression of silica-induced pulmonary toxicity is critical for the intervention and/or prevention of the adverse health effects associated with crystalline silica exposure. Rats were exposed to crystalline silica by inhalation at a concentration of 15 mg/m3, 6 hours/day, 5 days/week for 3, 6 or 12 weeks. At the end of each exposure time point, toxicity and global gene expression changes were determined in the lungs. In general, silica exposure resulted in pulmonary toxicity that was dependent on the duration of silica exposure. A significant and silica exposure time-dependent increase in lactate dehydrogenase activity and accumulation of alveolar macrophages and infiltrating neutrophils in the bronchoalveolar lavage fluid suggested crystalline silica-induced pulmonary toxicity in the rats. Histological changes indicative of pulmonary toxicity were detectable only in the lungs of rats that were exposed to silica for 6- or 12-weeks. Minimal, sub-acute pulmonary inflammation consisting mainly of macrophage accumulation and infiltration of neutrophils was seen in 2 out of 8 rats in the 6-week silica exposure group. Chronic active inflammation, type II pneumocyte hyperplasia, and fibrosis were detected following 12-weeks of silica exposure in all rat lungs. In addition, crystalline silica was visible in the lungs of the rats belonging to the 12-week exposure group. A significant increase in the number of neutrophils seen in the blood indicated silica-induced systemic inflammation in the rats. Microarray analysis of the global gene expression profiles of the rat lungs detected significant differential expression (FDR p <0.05 and fold change >1.5) of 38, 77 and 99 genes in the rats exposed to silica for 3-, 6- and 12-weeks, respectively, compared to the time-matched controls. Bioinformatics analysis of the differentially expressed genes identified significant enrichment of functions, networks and pathways related to inflammation, cancer, oxidative stress, fibrosis and tissue remodeling in the lungs of the silica exposed rats. Collectively, the results of our study provided insights into the molecular mechanisms underlying pulmonary toxicity following sub-chronic exposure to silica in rats. 36 samples were analyzed in this experiment. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 3 weeks. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 6 weeks. 6 rats were exposed to crystalline silica by inhalation 15 mg/m3, 6 hours/day, 5 days, 12 weeks. 18 rats served as controls (6 for each 3 week, 6 week, and 12 week exposure) and were exposed to air during treatment times. Lung gene expression profiling was performed using RNA isolated from rat lung samples.

Dataset Information

Impact of cellular crosstalk on the cytochrome expression in an in vitro test system relevant for the alveolar barrier

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets