Macrophages are a common phagocytic cell and a member of immune cells. It is a white blood cell located in a tissue derived from monocytes. It is characterized by plasticity and versatility. It plays an important role in clearing senescent or apoptotic cells, phagocytosis of immune-related complexes and pathogens, and maintenance of homeostasis. The phenotype and function of macrophages may be polarized by microenvironment.
3. Transcription Factors and Signaling Pathways that Affect Macrophage Polarization
The phenotype and functional polarization of macrophages are regulated by many factors. Signal transducers and transcriptional activators that affect macrophage polarization are as follows: STATs, interfering regulatory factors (IRFs), nuclear factors (NF-kappab), activating proteins (AP1), peroxisome proliferators activating receptors (PPAR-gamma), and cAMP response element binding protein (CREB). They interact with each other to regulate the phenotype of macrophages.
Figure 3 Factors affecting macrophage polarization
The Notch pathway regulates macrophage polarization by controlling gene expression, thereby modulating the immune response.
Myelo-derived macrophages activate Notch1 and NF-kappab under the stimulation of LPS and toll-like receptors, thus polarized M1-type macrophages. One molecular mechanism of Notch1-dependent M1 polarization is the transactivation of the M1 type gene by NICD1, resulting in the effect of Notch1 activation . In addition, IRF5 is associated with M1 macrophage polarization and can be stimulated by inflammation in atherosclerosis , and nitrification of IRF5 protein leads to inhibition of IRF5-targeted M1 macrophage signaling gene activation .
The JAK-STAT signaling pathway is also closely related to the phenotypic activity of macrophages . IFN (interferon) works through this signaling pathway. IFN-γ can induce polarization of M1 macrophages. The role of IFN-α/IFN-β-mediated signaling pathways in macrophage polarization is not well understood, but it is known to enhance anti-inflammatory effects under certain conditions.
PI3K pathway plays an important role in the survival of macrophages . Different AKt kinases have different effects on macrophage polarization. Among them, AKt1 can be activated by PI3K, and the ablation of AKt1 leads to polarization of M1-type macrophages, while the ablation of AKt2 leads to polarization of M2-type macrophages .
In addition to the above signaling pathways, mitochondrial biosynthesis also plays an important role in macrophage polarization . In addition, HGF promotes the transformation of macrophages from M1 to M2 by activating the JAK2/STAT3 signaling pathway. But its molecular mechanism is not clear.
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