Cecil Alicia A, Klemsz Michael J
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
J Leukoc Biol. 2004 Mar;75(3):560-8. doi: 10.1189/jlb.0803375. Epub 2003 Dec 23.
Although interferon-gamma (IFN-gamma) induces the transporter associated with antigen processing (Tap)-1 expression in macrophages, cooperation with lipopolysaccharide signaling through Toll-like receptor 4 (TLR4) accelerates the kinetics and increases the overall levels of this gene. In this report, we show that peptidoglycan signaling through TLR2 and bacterial CpG DNA signaling through TLR9 are functionally equivalent at synergizing with IFN-gamma in regulating Tap-1 expression in macrophages. Activation of the p38 mitogen-activated protein kinase is necessary for this response, which correlates with increased phosphorylation of signal transducer and activator of transcription-1 on serine 727. Activation of p38, however, is not sufficient, as this signaling event does not affect the response to IFN-gamma in HeLa cells. The cooperation between these different signaling pathways also requires membrane fluidity. These data suggest that macrophages possess an ability to coordinate the signaling between the IFN-gamma and TLR receptors.
虽然干扰素-γ（IFN-γ）可诱导巨噬细胞中与抗原加工相关的转运体（Tap）-1表达，但通过Toll样受体4（TLR4）与脂多糖信号传导协同作用可加速其动力学过程并提高该基因的总体水平。在本报告中，我们表明通过TLR2的肽聚糖信号传导和通过TLR9的细菌CpG DNA信号传导在与IFN-γ协同调节巨噬细胞中Tap-1表达方面功能等效。p38丝裂原活化蛋白激酶的激活对于此反应是必需的，这与信号转导和转录激活因子-1在丝氨酸727上磷酸化增加相关。然而，p38的激活并不充分，因为此信号事件不影响HeLa细胞对IFN-γ的反应。这些不同信号通路之间的协同作用也需要膜流动性。这些数据表明巨噬细胞具有协调IFN-γ和TLR受体之间信号传导的能力。
