Department of Neurology, University of Göttingen, Robert-Koch-Strasse 40, Göttingen, Germany.
Glia. 2010 Feb;58(3):367-76. doi: 10.1002/glia.20929.
Microglia express Toll-like receptors (TLRs) that recognize invading pathogens as well as endogenous proteins such as fibronectin under nonphysiological conditions. Here, we demonstrated that fibronectin stimulates murine microglia in culture in a dose-dependent manner: microglial cells secreted proinflammatory cytokines and chemokines and increased phagocytosis of Escherichia coli DH5alpha and E. coli K1 strains. Low levels of fibronectin exerted a synergistic effect on the release of proinflammatory compounds by microglia co-stimulated with agonists for TLR1/2 (Pam(3)CSK(4)) or TLR9 (CpG DNA), but not in combination with the TLR4 agonist lipopolysaccharide (LPS). Phagocytosis of bacterial strains was moderately enhanced when microglia was co-stimulated with high concentrations of fibronectin and one pathogen-derived TLR agonist. In conclusion, fibronectin increased proinflammatory and phagocytotic functions in microglia and partially synergized with microbial TLR agonists.
小胶质细胞表达 Toll 样受体 (TLRs)，这些受体可以识别入侵的病原体以及非生理条件下的内源性蛋白质，如纤维连接蛋白。在这里，我们证明纤维连接蛋白以剂量依赖的方式刺激培养中的小鼠小胶质细胞：小胶质细胞分泌促炎细胞因子和趋化因子，并增加对大肠杆菌 DH5alpha 和大肠杆菌 K1 菌株的吞噬作用。低水平的纤维连接蛋白与 TLR1/2（Pam(3)CSK(4)）或 TLR9（CpG DNA）激动剂共同刺激小胶质细胞时，对促炎化合物的释放具有协同作用，但与 TLR4 激动剂脂多糖 (LPS) 无协同作用。当小胶质细胞与高浓度的纤维连接蛋白和一种病原体衍生的 TLR 激动剂共同刺激时，细菌菌株的吞噬作用适度增强。总之，纤维连接蛋白增强了小胶质细胞的促炎和吞噬功能，并与微生物 TLR 激动剂部分协同作用。
