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Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard
- Source :
- Ann N Y Acad Sci
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Nitrogen mustard (NM) and sulfur mustard are cytotoxic alkylating agents that cause severe and progressive damage to the respiratory tract. Evidence indicates that macrophages play a key role in the acute inflammatory phase and the later resolution/profibrotic phase of the pathogenic response. These diverse roles are mediated by inflammatory macrophages broadly classified as M1 proinflammatory and M2 anti-inflammatory that sequentially accumulate in the lung in response to injury. The goal of the present study was to identify signaling mechanisms contributing to macrophage activation in response to mustards. To accomplish this, we used RNA sequencing to analyze the gene expression profiles of lung macrophages isolated 1 and 28 days after intratracheal exposure of rats to NM (0.125 mg/kg) or phosphate-buffered saline control. We identified 641 and 792 differentially expressed genes 1 and 28 days post-NM exposure, respectively. These genes are primarily involved in processes related to cell movement and are regulated by cytokines, including tumor necrosis factor-α, interferon-γ, and interleukin-1β. Some of the most significantly enriched canonical pathways included STAT3 and NF-κB signaling. These cytokines and pathways may represent potential targets for therapeutic intervention to mitigate mustard-induced lung toxicity.
- Subjects :
- Male
0301 basic medicine
Biology
Article
General Biochemistry, Genetics and Molecular Biology
Proinflammatory cytokine
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
History and Philosophy of Science
Macrophages, Alveolar
Pulmonary fibrosis
Gene expression
medicine
Animals
Cytotoxic T cell
Chemical Warfare Agents
Mechlorethamine
RNA-Seq
Rats, Wistar
Inflammation
Lung
General Neuroscience
Sulfur mustard
Lung Injury
medicine.disease
Nitrogen mustard
Rats
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
chemistry
030220 oncology & carcinogenesis
Cancer research
Tumor necrosis factor alpha
Subjects
Details
- ISSN :
- 17496632 and 00778923
- Volume :
- 1480
- Database :
- OpenAIRE
- Journal :
- Annals of the New York Academy of Sciences
- Accession number :
- edsair.doi.dedup.....7881d11d6c3904fbe1902969c9e3aedb