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Interleukin-1 beta as a driver of renal NGAL production

机译:白细胞介素-1β作为肾NGAL生产的驾驶员

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Neutrophil gelatinase-associated lipocalin (NGAL) is increasingly regarded as a biomarker of acute kidney injury, or kidney injury in general, but the stimuli responsible for its production are incompletely understood. This study tested the relationship between the pro-inflammatory cytokine interleukin-l beta (IL-1 beta) and both circulating and renal NGAL, using chronic subcutaneous infusion of IL-113 in mice and tissue culture of renal cell lines. Following a 14-day subcutaneous infusion of vehicle or IL-1 beta (10 ng/h) in male C57B1/6 mice, a striking positive correlation (r(2) = 0.94; P < 0.01) was observed between plasma IL-1 beta and NGAL concentrations. NGAL was markedly increased in the kidneys of IL-1 beta-infused mice compared with vehicle-treated mice, both at the protein and mRNA level, indicating increased local as well as systemic production of NGAL. Immunohistochemical staining revealed prominent increases of NGAL in the proximal tubular epithelium of IL-l beta infused mice. These effects occurred in the absence of overt renal injury, with plasma creatinine concentration not significantly different between groups. Further showing that IL-1 beta has a direct effect on NGAL production by tubular epithelial cells, exposure of a proximal tubular cell line (HK-2 cells) and a cortical collecting duct principal cell line (mpkCCD cells) to IL-1 beta for 24 h produced a significant increase of NGAL mRNA levels (> 30-fold). These data indicate IL-1 beta serves as a powerful stimulus for renal production of NGAL. (C) 2016 Elsevier Ltd. All rights reserved.
机译:中性粒细胞明胶酶相关的脂素(NGAL)越来越多地被视为急性肾损伤的生物标志物,或者肾损伤一般,但对其生产的刺激是不完全理解的。本研究测试了促炎细胞因子白细胞介素-Lβ(IL-1β)与循环和肾NGAL之间的关系,使用肾细胞系的小鼠和组织培养的慢性皮下输注IL-113。在雄性C57B1 / 6小鼠中的载体或IL-1β(10ng / h)的14天皮下注射后,在血浆IL-1之间观察到醒目的正相关(R(2)= 0.94; p <0.01) β和Ngal浓度。在蛋白质和mRNA水平的与载体处理的小鼠相比,IL-1β注入小鼠的肾脏中,NGAL显着增加,所述蛋白质和mRNA水平,表明局部增加以及NGAL的全身生产。免疫组织化学染色在IL-Lβ注入小鼠的近端管状上皮中显示出突出的NGAL。这些效果在没有公开肾损伤的情况下发生,血浆肌酐浓度在组之间没有显着差异。进一步表明IL-1β通过管状上皮细胞对Ngal产生的直接影响,近端管状细胞系(HK-2细胞)和皮质收集管道主细胞系(MPKCCD细胞)对IL-1 BETA的曝光24小时产生NGAL mRNA水平(> 30倍)的显着增加。这些数据表明IL-1β用作NGAL的肾脏生产的强大刺激。 (c)2016 Elsevier Ltd.保留所有权利。

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