Neutrophilic granule protein (NGP) belongs to the cystatin superfamily. Even though this superfamily is critically involved in cancer biology and adaptive immunity, the relationship of macrophage NGP to inflammation and phagocytosis remains poorly understood. In this study, we observed a significant increase of NGP in peritoneal macrophages (PMs) isolated from mice challenged with E. coli or lipopolysaccharide (LPS), as judged by NGP mRNA microarray. We also found changes in NGP to be mainly Toll-like receptor 4 (TLR4)-dependent. By western blot and electrophoretic mobility shift assay, we demonstrated NGP overexpression to reduce TNF-α and IL-1β production by LPS-induced RAW264.7 cells (RAW) via suppression of the NF-κB (p65 and p50) signalling pathway, rather than the JNK1/AP-1 (fos and jun) signalling pathway. NGP overexpression by LPS-induced RAW also induced IL-10, an anti-inflammatory cytokine, which was partially involved in the anti-inflammatory effect produced by NGP overexpression. Moreover, upregulated NGP enhanced the phagocytosis of E. coli by RAW. Taken together, these results demonstrated NGP to be an important host defense component that regulates inflammatory responses and phagocytosis by activated macrophages. As such, NGP may be useful for the treatment of inflammatory based disease.

中文翻译：

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中性粒细胞蛋白 (NGP) 减弱脂多糖诱导的炎症反应并增强巨噬细胞对细菌的吞噬作用

中性粒细胞蛋白 (NGP) 属于胱抑素超家族。尽管这个超家族与癌症生物学和适应性免疫密切相关，但巨噬细胞 NGP 与炎症和吞噬作用的关系仍然知之甚少。在这项研究中，我们观察到从用大肠杆菌或脂多糖 (LPS) 攻击的小鼠分离的腹膜巨噬细胞 (PM) 中 NGP 显着增加，如通过 NGP mRNA 微阵列判断。我们还发现 NGP 的变化主要依赖于 Toll 样受体 4 (TLR4)。通过蛋白质印迹和电泳迁移率变化测定，我们证明 NGP 过表达通过抑制 NF-κB（p65 和 p50）信号通路来减少 LPS 诱导的 RAW264.7 细胞（RAW）产生的 TNF-α 和 IL-1β，而不是与 JNK1/AP-1（fos 和 jun）信号通路相比。LPS 诱导的 RAW 过表达 NGP 还诱导了 IL-10，一种抗炎细胞因子，其部分参与了 NGP 过表达产生的抗炎作用。此外，上调的 NGP 增强了 RAW 对大肠杆菌的吞噬作用。总之，这些结果表明 NGP 是一种重要的宿主防御成分，可通过活化的巨噬细胞调节炎症反应和吞噬作用。因此，NGP 可用于治疗基于炎症的疾病。这些结果表明 NGP 是一种重要的宿主防御成分，通过活化的巨噬细胞调节炎症反应和吞噬作用。因此，NGP 可用于治疗基于炎症的疾病。这些结果表明 NGP 是一种重要的宿主防御成分，通过活化的巨噬细胞调节炎症反应和吞噬作用。因此，NGP 可用于治疗基于炎症的疾病。