Lack of RNase L attenuates macrophage functions.
Lack of RNase L attenuates macrophage functions.
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DOI：
10.1371/journal.pone.0081269
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhou A
中科院分区：
文献类型：
--
作者：
Yi X;Zeng C;Liu H;Chen X;Zhang P;Yun BS;Jin G;Zhou A
巨噬细胞是针对微生物感染的先天免疫的主要细胞类型之一。据认为，巨噬细胞表达的促炎基因，如肿瘤坏死因子-α (TNF-α)、白细胞介素 (IL)-1β、IL-6 和环氧合酶-2 (Cox-2) 对于先天免疫和适应性免疫的激活也至关重要。 RNase L 是一种干扰素 (IFN) 诱导酶，在巨噬细胞中高度表达。已证明 RNase L 调节某些炎症基因的表达。然而，其在巨噬细胞功能中的作用很大程度上未知。骨髓源性巨噬细胞 (BMM) 由 RNase L+/+ 和 -/− 小鼠产生。使用 Transwell 迁移测定分析 BMM 的迁移。使用异硫氰酸荧光素 (FITC)-葡聚糖 40,000 和 FITC-E 评估巨噬细胞的内吞作用和吞噬作用。分别是大肠杆菌。通过Western Blot和ELISA测定炎症基因的表达。 Cox-2 的启动子活性通过荧光素酶报告基因测定来测量。缺乏 RNase L 会显着降低 M-CSF 诱导的 BMM 迁移，但 GM-CSF 和趋化因子 C-C 基序配体 2 (CCL2) 诱导的 BMM 迁移程度较小。有趣的是，RNase L缺陷的BMM表现出对FITC-葡聚糖40,000的内吞活性显着降低，但在相同条件下对其对FITC-细菌的吞噬活性没有任何明显影响。 RNase L 影响与细胞迁移和炎症相关的某些基因的表达，例如转化生长因子 (TGF)-β、IL-1β、IL-10、CCL2 和 Cox-2。此外，Cox-2启动子的功能分析表明，RNase L在转录水平上调节巨噬细胞中Cox-2的表达。总而言之，我们的研究结果提供了直接证据，表明 RNase L 通过调节巨噬细胞功能有助于先天免疫。
Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL–6, and cyclooxygenase-2 (Cox-2) by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN) inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown. Bone marrow-derived macrophages (BMMs) were generated from RNase L+/+and −/− mice. The migration of BMMs was analyzed by using Transwell migration assays. Endocytosis and phagocytosis of macrophages were assessed by using fluorescein isothiocyanate (FITC)-Dextran 40,000 and FITC-E. coli bacteria, respectively. The expression of inflammatory genes was determined by Western Blot and ELISA. The promoter activity of Cox-2 was measured by luciferase reporter assays. Lack of RNase L significantly decreased the migration of BMMs induced by M-CSF, but at a less extent by GM-CSF and chemokine C-C motif ligand-2 (CCL2). Interestingly, RNase L deficient BMMs showed a significant reduction of endocytic activity to FITC-Dextran 40,000, but no any obvious effect on their phagocytic activity to FITC-bacteria under the same condition. RNase L impacts the expression of certain genes related to cell migration and inflammation such as transforming growth factor (TGF)-β, IL-1β, IL-10, CCL2 and Cox-2. Furthermore, the functional analysis of the Cox-2 promoter revealed that RNase L regulated the expression of Cox-2 in macrophages at its transcriptional level. Taken together, our findings provide direct evidence showing that RNase L contributes to innate immunity through regulating macrophage functions.
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