M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia

摘要: Microglia are the primary immune cells of brain whose phenotype largely depends on their surrounding micro-environment. respond to a multitude soluble molecules produced by variety cells. Macrophage colony-stimulating factor (M-CSF) is cytokine found in receptor expressed microglia. Previous studies suggest critical role for M-CSF development and normal functioning as well several disease processes involving neuroinflammation. Using biopsy tissue from patients with intractable temporal epilepsy autopsy tissue, we cultured adult human microglia investigate response M-CSF. Mixed glial cultures were treated 25 ng/ml 96 hours. Proliferation phagocytosis assays, high through-put immunocytochemistry, microscopy image analysis performed microglial function. We that was markedly changed following exposure A greater number present M-CSF- percentage proliferating (BrdU Ki67-positive) greatly increased. changes protein expression occurred treatment, including increased transcription factors PU.1 C/EBPβ, DAP12 adaptor protein, (CSF-1R) IGF-1 receptor, reduced HLA-DP, DQ, DR antigen presentation protein. Furthermore, distinct morphological change observed elongation processes. These accompanied functional increase Aβ1-42 peptide. show here dramatically influences results pave way future investigation M-CSF-related targets therapeutic benefit.