GSE184840
15-Lipoxygenase-2 Deficiency Induces a Dysfunction in Macrophages that can be Restored by Salidroside
15-Lipoxygenase-2 (15-LOX-2) is thought to regulate inflammation and immunological function; however, its mechanisms of action are still unclear. Furthermore, it has been reported that salidroside has anti-inflammatory properties, but its role in macrophage function is not yet understood. In this study, we aimed to determine how 15-LOX-2 expression levels affect the function of macrophages and the effect of salidroside on 15-LOX-2-deficient macrophages. We used multiple functional genetic strategies to determine 15-LOX-2 function in macrophages. 15-LOX-2 deficiency promoted phagocytosis and the proliferation of macrophages and impaired their apoptosis. Mechanistically, the expression levels of cyclophilin B (CypB) were upregulated in 15-LOX-2-deficient Ana-1 macrophages, whereas those of caspase-3 were downregulated. Furthermore, RNA-seq analysis showed that inflammation, complement, and TNF-a signaling pathways were all activated in 15-LOX-2-deficient Ana-1 macrophages. Treatment of 15-LOX-2-deficient macrophages with salidroside, a natural product derived from Rhodiola species, effectively reversed the effects of 15-LOX-2 deficiency on caspase-3 and CypB levels, as well as on apoptosis and proliferation. In conclusion, our study shows a newly identified link between 15-LOX-2 deficiency and salidroside in regulating macrophage survival, proliferation, and function. Salidroside may be a promising therapeutic strategy for treating inflammation-related diseases resulting from 15-LOX-2 deficiency. Overall design: RNA-seq data of 15-LOX-2 deficient Ana-1 macrophage