Comprehensive analysis of the effects of damage-associated molecules derived from a canine tumor cell on macrophages

Dying or damaged cells release their cellular components extracellularly if they are not eradicated by the immune system appropriately. Since aberrant exposure of damage-associated molecules to the immune system is often linked to the pathogenesis of inflammation and cancer, elucidating which and how sterile immune responses are induced by damage-associated molecules is of great importance. In this study, we show that prostaglandin E2 (PGE2) is produced in necrotic supernatants from several types of canine tumor cell lines. Inhibition of PGE2 production by treatment of indomethacin, a potent inhibitor for cyclooxygenase enzymes, enhances induction of Tnf mRNA expression in RAW264.7 cells by necrotic supernatants. These results prompted us to investigate which genes are induced by damage-associated molecules by comprehensive gene expression analysis.We performed RNA-sequencing analysis by using total RNA from RAW264.7 cells treated with necrotic supernatant derived from Sora cells, which is canine urothelial carcinoma cell lines, in combination with indomethacin treatment.