Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy
Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy
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IgA 肾病患者分泌型 IgA 刺激人系膜细胞的增殖和细胞因子产生
DOI：
10.1159/000430151
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Liu, Zhangsuo
中科院分区：
文献类型：
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作者：
Liang, Yan;Zhang, Junjun;Liu, Zhangsuo
背景/目的：IgA 肾病 (IgAN) 是原发性肾小球肾炎最常见的形式，并且经常因粘膜感染而加重。分泌型IgA（SIgA）是粘膜免疫中占主导地位的免疫球蛋白，在IgAN中沉积于系膜中。 SIgA 对系膜细胞的生物学效应知之甚少。方法：检测 IgAN 患者冰冻肾切片中 SIgA 的沉积，并分析 SIgA 沉积与患者特征之间的关联。比较了 SIgA 和聚合 IgA (pIgA) 对人肾系膜细胞的生物学效应。我们还研究了microRNA调节SIgA对系膜细胞炎症作用的分子机制。结果：176例患者中，55例有SIgA沉积，与无SIgA沉积的患者相比，感染史和血尿发生率较高，血清胱抑素C、β2微球蛋白、血尿素氮和牛津分类T分级较低。与健康志愿者的 SIgA 相比，SIgA 刺激系膜细胞的增殖率更高，白细胞介素 (IL)-6、IL-8、单核细胞趋化蛋白 1、转化生长因子-β1 和纤连蛋白的产量也更高。 SIgA刺激的系膜细胞的增殖和细胞因子的产生显着低于pIgA刺激的。 miR-16 靶向 IL-6 的 3'非翻译区并抑制其在 SIgA 诱导的系膜细胞中的翻译。结论：SIgA对系膜细胞的生物学作用与pIgA不同。 SIgA 刺激系膜细胞增殖和促炎细胞因子的产生。 IL-6 的产生受系膜细胞中 miR-16 的调节。
Background/Aims: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, and often aggravates by mucosal infection. Secretory IgA (SIgA) is the dominant immunoglobulin in mucosal immunity, and is deposited in the mesangium in IgAN. The biological effects of SIgA on mesangial cells are poorly understood. Methods: Deposition of SIgA in frozen renal sections from IgAN patients was detected and the association between deposition of SIgA and patients characteristics was analyzed. The biological effects of SIgA and polymeric IgA (pIgA) on human renal mesangial cells were compared. We also studied the molecular mechanism of microRNA regulating the inflammatory effects of SIgA on mesangial cells. Results: Fifty-five of 176 patients had SIgA deposition with higher incidence of infection history and hematuria, lower serum cystatin C, β2 microglobulin, blood urea nitrogen and T-grade in the Oxford classification, compared with patients without SIgA deposition. SIgA stimulated mesangial cells at a higher ratio of proliferation and higher production of interleukin (IL)-6, IL-8, monocyte chemotactic protein 1, transforming growth factor-β1 and fibronectin, compared with SIgA from healthy volunteers. The proliferation and cytokines production in mesangial cells stimulated by SIgA were significantly lower than that stimulated by pIgA. miR-16 targeted the 3′-untranslated region of IL-6 and suppressed its translation in mesangial cells induced by SIgA. Conclusions: The biological effects of SIgA on mesangial cells differ from those of pIgA. SIgA stimulates mesangial cell proliferation and production of proinflammatory cytokines. IL-6 production is regulated by miR-16 in mesangial cells.