Dataset Information

Ozone exposure in the fibrotic Surfactant Protein-C mutant lung

ABSTRACT: Environmental exposure and genetic mutations are principal contributors in the initiation and exacerbation of fibrogenic injury. We have established a murine model of lung remodeling triggered by inducible expression of the most common PF-linked mutation in the Surfactant Protein-C gene (SP-C). The mutation at position 73 is the most common among >60 clinically identified. We have previously deposited a single-cell sequencing dataset of lung tissues at times coordinated with peak inflammation (14 d post induction) and established fibrotic remodeling (42 d post induction). This work allowed annotation of fibrogenic signals emanating from the epihtelial, mesenchymal, and immune compartment. We then set aim to expand our investigation to examine the effects of ozone exposure in the fibrotic lung (42 days post mutant induction). Ozone is a ubiquitous environmental toxicant known to cause focal parenchymal injury and transient myeloid inflammation. Fibrotic mice exposed to ozone (0.8 ppm, 3 h hours) promoted shifts in myeloid and lymphoid inflammatory cells, measured by flow cytometry. This transcriptomics dataset show aberrant activation among monocyte-derived macrophages. Together, these results suggest that ozone exposure in the fibrotic lung is linked to non-canoncial activation of peripherally-derived populations and that these cells should be further examined for their pro-fibrotic phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE343116 | GEO | 2026/09/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Ozone is a major air pollutant in highly populated areas. High levels of ambient ozone have been associated with decreased lung function and increased exacerbations of asthma in children and adults. However, the effects of ozone on the newbornM-bM-^@M-^Ys lung are largely unknown. This study was aimed at profiling the newborn lung response to ozone at the transcriptome level to define the impact of ozone pollutant on the developing postnatal lung. Newborn mice were exposed to ozone or filtered normal air for 3 h. Total RNA was isolated from lung tissues at 6 and 24 h after completion of exposure and was subjected to gene expression analysis using Whole Mouse Genome Gene Expression 4X44K Microarrays (G2519F-014868, Agilent Technologies). Transcriptome analysis of the postnatal lung indicated that 455 genes were down-regulated and 166 genes were up-regulated by at least 1.5 fold at 6 h post-ozone exposure (t-test, p<0.05). At 24 h post exposure, 543 genes were down-regulated and 323 genes were up-regulated in the lungs of ozone-exposed newborn mice, compared to filtered air-exposed newborn mice (t-test, p<0.05). After controlling for false discovery rate, 50 genes were significantly down-regulated and only 4 genes were up-regulated at 24 h post ozone-exposure (q<0.05). Gene ontology enrichment analysis revealed that cell cycle-associated functions including cell division/proliferation, cellular assembly and organization were the predominant pathways negatively regulated by ozone exposure. These findings suggest that elevated ozone pollution may interfere with lung development and growth in the early age. Three-day old BALB/c mice were exposed for 3 h to ozone (1000 parts per billion). Age-matching littermate controls were exposed for 3 h to filtered normal air. Whole lung tissue was collected 6 and 24 h after completion of exposure to ozone or filtered air and was subjected to microarray analysis. Each time point was performed separately with its own filtered air littermate controls. Pups were cross-fostered during exposure so that all pups were with a dam during exposure. A total of 6-8 mice were initially included in each group and time point. Of these, n=4 mouse lungs were randomly selected for use in gene expression analysis.

Project description:Rationale: Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases TLR4-mediated response to subsequent stimulation with lipopolysaccharide (LPS). To further explore the pulmonary innate immune response to ozone exposure, we investigated the effect of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Methods: Bronchoalveolar lavage (BAL) and lungs were harvested from C57Bl/6 mice after exposure to ozone or filtered air followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the BAL, surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. Results: We demonstrate an increased BAL cell influx, increased IL-6 and KC, and decreased MIP-1α and TNF-α in response to Pam3CYS as a result of ozone pre-exposure. We also observed increased cell surface expression of TLR4, TLR2 and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in expression of genes related to injury repair and cell cycle as a result of ozone exposure. When comparing Pam3CYS treated animals to saline treated animals with or without ozone, genes associated with inflammation were significantly increased. Potentially novel ozone exposure candidate genes (CCK, RELM-α and β) were identified. Conclusion: Our results extend previous findings with ozone/LPS to other TLRs PAMPs and suggest that ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level. Mice were exposed to either 2ppm ozone or filtered air (FA) for 3 hours. 24 hours following ozone exposure, mice from either the ozone or FA group were treated intratracheally with either 100ug of Pam3CYS in saline or saline alone. Animals were euthanized 4 or 24 hours post-Pam3CYS exposure. RNA from whole lung tissue from 4 animals per group was profiled.

Dataset Information

Ozone exposure in the fibrotic Surfactant Protein-C mutant lung

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets