Pearl-Yafe Michal, Fabian Ina, Halperin Drora, Flatau Edith, Werber Sara, Shalit Itamar
Department of Cell and Developmental Biology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Shock. 2007 Mar;27(3):226-31. doi: 10.1097/01.shk.0000239765.80033.37.
In human neutrophils, interferon (IFN)-gamma enhanced the expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Lipopolysaccharide alone did not affect TLR4 expression, but costimulation with IFN-gamma and LPS induced higher levels of TLR4 expression than stimulation with IFN-gamma alone. Using the protein synthesis inhibitor cycloheximide and measuring the expression of CD35 in neutrophils stimulated with IFN-gamma and LPS alone or in combination, we could demonstrate that IFN-gamma enhances TLR4 by de novo protein synthesis, whereas the addition of LPS acts synergistically by enhancing vesicular mobilization to the cell surface. Costimulation with IFN-gamma and LPS induced neutrophil activation and enhanced secretion of the cytokines, interleukin (IL)-8, IL-1beta, tumor necrosis factor-alpha, and IL-12 p70, and phagocytosis of latex beads, processes that were blocked by a monoclonal antibody specific for TLR4. These data suggest that IFN-gamma primes neutrophils to respond to LPS.
在人类中性粒细胞中，γ干扰素（IFN-γ）增强了Toll样受体4（TLR4）的表达，TLR4是细菌脂多糖（LPS）信号受体复合物的关键组成部分。单独的脂多糖不影响TLR4的表达，但IFN-γ与LPS共同刺激诱导的TLR4表达水平高于单独用IFN-γ刺激。使用蛋白质合成抑制剂环己酰亚胺，并检测单独或联合使用IFN-γ和LPS刺激的中性粒细胞中CD35的表达，我们可以证明IFN-γ通过从头合成蛋白质来增强TLR4，而添加LPS则通过增强向细胞表面的囊泡转运起协同作用。IFN-γ与LPS共同刺激诱导中性粒细胞活化，并增强细胞因子白细胞介素（IL）-8、IL-1β、肿瘤坏死因子-α和IL-12 p70的分泌，以及乳胶珠的吞噬作用，这些过程被针对TLR4的单克隆抗体阻断。这些数据表明，IFN-γ使中性粒细胞对LPS产生反应。
