Polyinosinic acid induces TNF and NO production as well as NF-κB and AP-1 transcriptional activation in the monocyte-macrophage cell line RAW 264.7
Polyinosinic acid induces TNF and NO production as well as NF-κB and AP-1 transcriptional activation in the monocyte-macrophage cell line RAW 264.7
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DOI：
10.1007/s00011-005-1359-4
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发表时间：
2005-08-01
影响因子：
6.7
通讯作者：
Lazo, PS
中科院分区：
文献类型：
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作者：
Campa, VM;Iglesias, JM;Lazo, PS
目的：本研究评估了聚肌苷酸（poly I）诱导的小鼠单核-巨噬细胞系RAW 264.7中的活化，其导致炎性表型。材料：RAW 264.7和WEHI 164细胞系。激活过程的特征是获得成熟的巨噬细胞形态并产生炎症介质肿瘤坏死因子（TNF）和一氧化氮（NO）。poly I的激活具有独特的特征。因此，由于抑制性NF-κ B（I κ B）β的长期降解，聚I诱导核因子κ B（NF-κ B）转录活性的增加，而脂多糖（LPS）诱导I κ B α和I κ B β的降解。Poly I还诱导激活蛋白1（AP-1）转录活性的增加，这可能是由于丝裂原激活蛋白激酶（MAPK）ERK、Jun N末端激酶（INK）和p38的激活。硫酸葡聚糖（DS）有效地抑制了poly I诱导的激活，包括炎症介质的产生。硫酸葡聚糖还抑制聚I刺激的细胞中AP-1和NF-κ B的转录活性。RAW 264.7细胞表达巨噬细胞清道夫受体1（MSR 1）I型和MSR 1 II型，不同的上调后，与聚I.结论：结果表明，众所周知的清道夫受体的阻滞剂聚I激活巨噬细胞产生TNF和NO，触发特定的信号转导途径。
Objective: This study evaluates the poly inosinic acid (poly I)-induced activation in the murine monocyte-macrophage cell line RAW 264.7, which led to an inflammatory phenotype.Material: RAW 264.7, and WEHI 164 cell lines were used.Results: The activation process is characterized by the acquisition of a mature macrophage morphology and the production of inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO). The activation by poly I has distinctive features. Thus, poly I induced an increase in nuclear factor kappa B (NF-kappa B) transcriptional activity due to a long-term degradation of inhibitory NF-kappa B (I kappa B) beta while lipopolysaccharide (LPS) induced the degradation of both I kappa B alpha and I kappa B beta. Poly I also induced an increase in activator protein 1 (AP-1) transcriptional activity, possibly due to the activation of the mitogen activated protein kinases (MAPKs) ERK, Jun N terminal kinase (INK) and p38. Dextran sulphate (DS) efficiently inhibited the activation induced by poly I including the production of the inflammatory mediators. Dextran sulphate also inhibited AP-1 and NF-kappa B transcriptional activities in poly I-stimulated cells. RAW 264.7 cells express macrophage scavenger receptor 1 (Msr1) type I and Msr1 type II that are differently up-regulated upon treatment with poly I.Conclusions: The results presented demonstrate that the well-known blocker of scavenger receptors poly I activates macrophages to produce TNF and NO, triggering specific signal transduction pathways.