Cyclooxygenase gene (Ptgs) exchange and differentially regulated inflammatory pathways in peritoneal macrophages. Mus musculus

The aim of the current study was to characterize the differential inflammatory signaling pathway of COX isoforms during systemic inflammation in mice. Peritoneal macrophages from mice challenged with either lipopolysaccharide (2 mg/kg body weight, WT, COX-2>COX-1, COX-1>COX-2, and Reversa mice) or PBS (Control, WT mice) were harvested. RNA (100 ng) was used to determine gene expression changes utilizing pre-built Mouse Inflammation V2 CodeSets to carry out Nanostring analysis. Our results indicate inflammatory networks can be maintained by isoform exchange in inflamed macrophages. However, COX-1>COX-2 macrophages show reduced activation of inflammatory signaling pathways, indicating that COX-1 may be replaced by COX-2 within this complex milieu, but not vice versa. Overall design: A dose of 2 mg/kg lipopolysaccharide (LPS) (body weight), diluted in sterile PBS, was injected intraperitoneally into WT (annotated as WT+LPS), COX-2>COX-1, COX-1>COX-2, and Reversa mice (12-16 wk; n=6 each group). An equivalent volume of PBS alone was given to another group of WT mice (Control group, annotated as WT-LPS). At 6 h post-injection, peritoneal macrophages were harvested and extracted for RNA analysis.