Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Mediates p38 Mitogen-Activated Protein Kinase Activation and Signal Transduction in Peripheral Blood Mononuclear Cells from Patients with Lupus Nephritis
Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Mediates p38 Mitogen-Activated Protein Kinase Activation and Signal Transduction in Peripheral Blood Mononuclear Cells from Patients with Lupus Nephritis
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DOI：
10.1007/s10753-011-9396-3
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发表时间：
2012-06-01
期刊：
影响因子：
5.1
通讯作者：
Tang Rong
中科院分区：
文献类型：
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作者：
Liu Zhi-Chun;Zhou Qiao-Ling;Tang Rong
42例系统性红斑狼疮（SLE）患者，包括26例肾损害患者和16例无肾损害患者，以及20名健康对照者被纳入本研究。用p38抑制剂（SB 203580）或抗肿瘤坏死因子样弱凋亡诱导剂（TWEAK）mAb处理分离的外周血单核细胞（PBMC），有或没有植物血凝素/佛波醇肉豆蔻酸酯（PHA/PMA）刺激。Western blot检测PBMC中TWEAK和p38 MAPK蛋白表达，ELISA检测PBMC培养上清中IL-10和MCP-1的含量。结果表明，狼疮肾炎患者PBMC中TWEAK蛋白的表达明显高于无肾损害的SLE患者和健康对照组。PHA/PMA刺激可上调SLE患者PBMC中TWEAK和p-p38 MAPK的表达。抗TWEAK mAb处理下调PBMC中的TWEAK和p-p38 MAPK表达，以及上清液中的IL-10和MCP-1; SB 203580对PBMC中的细胞因子产生具有相同的作用，但对TWEAK的表达没有影响。提示PBMC中TWEAK-p38 MAPK-IL-10、MCP-1信号通路在狼疮性肾炎的发病中起重要作用。
Forty-two patients with systemic lupus erythematosus (SLE), including 26 patients with renal damage and 16 without, and 20 healthy controls were included in the study. The isolated peripheral blood mononuclear cells (PBMCs) were treated with a p38 inhibitor (SB203580) or anti-tumor necrosis factor-like weak inducer of apoptosis (TWEAK) mAb, with or without phytohemagglutinin/phorbol myristate acetate (PHA/PMA) stimulation. Western blot experiments were used to evaluate the protein expression of TWEAK and p38 MAPK in PBMCs .Next, the contents of interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) in the supernatant were measured by ELISA. The results showed that expression of TWEAK protein in PBMCs from lupus nephritis patients was significantly higher than that from SLE patients without renal damage and healthy controls. PHA/PMA simulation could upregulate the productions of TWEAK and p-p38MAPK in PBMCs from patients with SLE. Anti-TWEAK mAb treatment downregulated both TWEAK and p-p38 MAPK expression in PBMCs, as well as IL-10 and MCP-1 in the supernatant; SB203580 had the same effect on cytokine production in PBMC, but had no effect on the expression of TWEAK. Our results suggested that TWEAK-p38 MAPK-IL-10, MCP-1 signaling pathway in PBMC played an important pathogenic role in lupus nephritis.