Data from: Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation

Macrophages play a key role in ozone-induced lung injury by regulating
both the initiation and resolution of inflammation. These distinct
activities are mediated by pro-inflammatory and
anti-inflammatory/pro-resolution macrophages which sequentially accumulate
in injured tissues. Macrophage activation is dependent, in part, on
intracellular metabolism. Herein, we used RNA-sequencing (seq) to identify
signaling pathways regulating macrophage immunometabolic activity
following exposure of mice to ozone (0.8 ppm, 3 hr) or air control.
Analysis of lung macrophages using an Agilent Seahorse showed that
inhalation of ozone increased macrophage glycolytic activity and oxidative
phosphorylation at 24 and 72 hr post exposure. An increase in the
percentage of macrophages in the S phase of the cell cycle was observed 24
hr post ozone. RNA-seq revealed significant enrichment of pathways
involved in innate immune signaling and cytokine production among
differentially expressed genes at both 24 and 72 hr after ozone, while
pathways involved in cell cycle regulation were upregulated at 24 hr and
intracellular metabolism at 72 hr. An interaction network analysis
identified tumor suppressor 53 (TP53), E2F family of transcription factors
(E2Fs), Cyclin Dependent Kinase Inhibitor 1A (CDKN1a/p21), and Cyclin D1
(CCND1) as upstream regulators of cell cycle pathways at 24 hr and TP53,
nuclear receptor subfamily 4 group a member 1 (NR4A1/Nur77), and estrogen
receptor alpha (ESR1/ERα) as central upstream regulators of mitochondrial
respiration pathways at 72 hr. These results highlight the complex
interaction between cell cycle, intracellular metabolism, and macrophage
activation which may be important in the initiation and resolution of
inflammation following ozone exposure.