Stem cell factor induces polarization of microglia to the neuroprotective phenotype in vitro

Abstract

Microglia are classified mainly into the M1 or M2 phenotypes, which evoke either proinflammatory or neuroprotective responses. Given the association of microglia with the pathogenesis of neuronal diseases, they are in focus as therapeutic targets for the treatment of such conditions. Stem cell factor (SCF) is a ligand for the c-kit receptor, one of the differentiation factors for bone marrow cells. In this study, characteristics of SCF-activated microglia and their effects on neurons were analyzed to investigate the therapeutic potential of SCF in neuronal diseases. SCF was found to induce proliferation, migration, and phagocytosis of microglia. In addition, SCF-derived microglia showed a neuroprotective phenotype expressing anti-inflammatory cytokines, growth factors, and M2 markers as compared to the phenotype shown by granulocyte macrophage-colony stimulating factor-derived microglia expressing inflammatory cytokines and M1 markers. Furthermore, supernatant medium from SCF-activated microglia enhanced cell proliferation and protection from cell death in NSC-34 neuronal cells. We conclude that SCF modulates microglial functions and induces activation of the neuroprotective effects of microglia, which could be used for treatment of neuronal diseases.

Effective Antidepressant Chronotherapeutics (Sleep Deprivation and Light Therapy) Normalize the IL-1β:IL-1ra Ratio in Bipolar Depression

“…This observation supports the hypothesis that a reduction in the low-grade inflammation associated with major depression is part of the mechanism of action of TSD+LT, as suggested by previous clinical trials showing that effective antidepressant TSD activates gene expression pathways involved in cytokine signaling and immune function (Foo et al, 2019), and induces a robust increase of SCF (Benedetti et al, 2016a), which modulates microglial activity in the brain toward expressing antiinflammatory cytokines (Terashima et al, 2018) and in particular downregulates the microglial expression of IL-1β in response to pro-inflammatory signaling (Zhang and Fedoroff, 1998). These specific effects could contribute to the observed reduction in IL-1β and increase in IL-1ra observed in our patients.…”

Different Inflammatory Signatures in Alzheimer’s Disease and Frontotemporal Dementia Cerebrospinal Fluid

“…Previous studies have implicated a mismatch in NGF metabolism in AD, where higher levels of MMPs have been associated with an increased degradation of NGF and an increase in loss of cholinergic neurons [38]. Microglia exposed for SCF have shown an anti-inflammatory phenotype in vitro [39]. Intracellular signaling cascades in neurons and oligodendrocytes, caused by LIF, leads to neurosurvival.…”

SCF + G-CSF treatment in the chronic phase of severe TBI enhances axonal sprouting in the spinal cord and synaptic pruning in the hippocampus

“…Microglial cells express both SCF receptor and G-CSF receptor [ 2 , 82 , 84 ], supporting the possibility of SCF and G-CSF in regulating the function of microglia [ 2 , 72 ]. It has been shown that microglial cells play an important role in pruning synapses in both neuronal development and diseases [ 32 , 33 , 43 , 78 ].…”