Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard

L. Cody Smith, Alessandro Venosa, Andrew J. Gow, Jeffrey D. Laskin, Debra L. Laskin

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)146-154
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1480
Issue number1
DOIs
StatePublished - Nov 17 2020

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • History and Philosophy of Science

Keywords

  • RNA-seq
  • macrophages
  • pulmonary fibrosis
  • sulfur mustard
  • vesicants

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