Ölüm reseptörü aktivasyonunun primer insan monositlerinin M1 makrofajlarına dönüşmesine etkisinin transkriptomik analizi

TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and induces either apoptosis or survival. Inducing apoptosis selectively in malignant cells without affecting normal cells makes TRAIL a promising agent for cancer therapy. Macrophages play key roles in both innate immune response and tissue homeostasis. Monocytes differentiate into unpolarized macrophages (M0) which are polarized into M1 (pro-inflammatory) or M2 (anti-inflammatory) macrophages depending on the stimuli. The effect of TRAIL on monocytes/macrophages is poorly understood. In this study, the transcriptional effect of TRAIL signaling on the differentiation of primary human monocytes to M0 and M1 macrophages is investigated. Primary human monocytes were either treated or untreated during differentiation into macrophages then the cells were either polarized to M1 macrophages or kept as unpolarized. To uncover the transcriptional differences in the TRAIL-treated macrophage group, RNA-sequencing was employed and differentially expressed genes were validated by qPCR. In addition, the level of CXCL11 and TNF in the cell supernatant was analyzed by ELISA. TRAIL stimulation during macrophage differentiation increased the expression of CXCL9 and TNF, whereas it decreased the expression of CXCL8 and CXCL5 in M0 macrophages. Moreover, the expression of HGF and PACERR was decreased in M1 macrophages, whilst both mRNA and protein levels of TNF and the protein level of CXCL11 were enhanced. In summary, our results show that TRAIL-DR4/5 signaling activation during macrophage differentiation drives monocytes to differentiate into M1-like macrophages. Our study sheds new light on mechanisms of monocyte-to-macrophage differentiation by defining TRAIL as a new modulator. Keywords: Monocytes, macrophages, TRAIL, death receptorsDR4/5