Fasl uyarımının primer insan makrofajlarının M1, M2A, ve M2C polarizasyonuna etkisi

Macrophages, the body's first line of defense, play a pivotal role in inflammation. With the plasticity ability, macrophages can be polarized into classically-activated (M1) or alternatively-activated (M2) phenotypes with appropriate signals. While M1 macrophages are responsible for generating a pro-inflammatory response against pathogens or tumors, M2 macrophages induce the anti-inflammatory response such as tissue regeneration and angiogenesis. Death receptor Fas is a member of the TNF receptor superfamily. Binding of Fas Ligand (FasL) to its receptor Fas can initiate apoptosis or non-apoptotic mechanisms. Previous studies have shown that Fas/FasL interaction enhances the expression of pro-inflammatory factors by inducing non-apoptotic mechanisms rather than causing cell death in macrophages. However, there is no comprehensive study in the literature investigating the effect of Fas activation on human primary macrophage polarization. To investigate this effect primary human macrophages were polarized into M1, M2a, and M2c phenotypes in the presence or absence of soluble FasL. The effect of FasL stimulation on macrophage phenotype was analyzed by qPCR and flow cytometry. In conclusion, our results demonstrated that FasL stimulation did not alter M0 macrophage response. In M1 macrophages, while FasL stimulation increased the expression of proinflammatory markers at mRNA level, but not at protein level. FasL stimulation significantly reduced the expression of the M2a surface marker CD206 at protein level in M2a polarized macrophages. Finally, M2c polarization was not affected by FasL stimulation. Our findings suggest that FasL, whose expression increases in inflammatory diseases such as cancer, has no functional effect on primary human macrophage polarization.