Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo
Acute reactive oxygen species (ROS)-dependent effects of IL-1β, TNF-α, and IL-6 on the glomerular filtration barrier (GFB) in vivo
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DOI：
10.1152/ajprenal.00111.2015
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发表时间：
2015-11-01
影响因子：
4.2
通讯作者：
Rippe, Bengt
中科院分区：
文献类型：
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作者：
Sverrisson, Kristinn;Axelsson, Josefin;Rippe, Bengt
本研究旨在研究促炎细胞因子IL-1 β、TNF-alpha和IL-6对大鼠肾小球滤过屏障（GFB）渗透性的直接作用，并测试这些作用是否依赖于活性氧的释放。（ROS）。在麻醉的大鼠中，实现血液通路，并将左输尿管插管用于尿液收集。大鼠连续静脉输注IL-1 β（0.4和2 μ g.kg（-1）.h（-1））、TNF-α（0.4和2 μ g.kg（-1）.h（-1））或IL-6（4和8 μ g.kg（-1）.h（-1）），以及多分散FITC-Ficoll-70/400和菊粉1小时。通过高效分子排阻色谱法（HPSEC）分析血浆和尿液样本，以测定肾小球筛分系数（θ）。还评估了肾小球滤过率（GFR）（Cr-51-EDTA）。在单独的实验中，在细胞因子输注之前和期间给予超氧化物清除剂tempol（30 mg mu g.kg（-1）.h（-1））。IL-1 β和TNF-α导致肾小球对大分子（Ficoll（50-80埃））的渗透性快速、部分可逆增加，在5-30分钟达到峰值，而IL-6导致渗透性逐渐增加，在60分钟达到平稳。Tempol几乎完全消除了细胞因子输注的肾小球渗透性效应。总之，IL-1 β，TNF-α和IL-6，当全身灌注时，引起肾小球通透性的立即和部分可逆的增加，这可以被超氧化物清除剂tempol抑制，这表明ROS在GFB中急性精氨酸诱导的通透性变化中的重要作用。
This study was performed to investigate the immediate actions of the proinflammatory cytokines IL-1 beta, TNF-alpha, and IL-6 on the permeability of the glomerular filtration barrier (GFB) in rats and to test whether these actions are dependent upon the release of reactive oxygen species (ROS). In anesthetized rats, blood access was achieved and the left ureter was cannulated for urine collection. Rats were continuously infused intravenously with either IL-1 beta (0.4 and 2 mu g.kg(-1).h(-1)), TNF-alpha (0.4 and 2 mu g.kg(-1).h(-1)), or IL-6 (4 and 8 mu g.kg(-1).h(-1)), together with polydisperse FITC-Ficoll-70/400 and inulin for 1 h. Plasma and urine samples were analyzed by high performance size exclusion chromatography (HPSEC) for determination of glomerular sieving coefficients (theta). The glomerular filtration rate (GFR) was also assessed (Cr-51-EDTA). In separate experiments, the superoxide scavenger tempol (30 mg mu g.kg(-1).h(-1)) was given before and during cytokine infusions. IL-1 beta and TNF-alpha caused rapid, partly reversible increases in glomerular permeability to large molecules (Ficoll(50-80 angstrom)), peaking at 5-30 min, while IL-6 caused a more gradual increase in permeability, leveling off at 60 min. Tempol almost completely abrogated the glomerular permeability effects of the cytokines infused. In conclusion IL-1 beta, TNF-alpha, and IL-6, when infused systemically, caused immediate and partly reversible increases in glomerular permeability, which could be inhibited by the superoxide scavenger tempol, suggesting an important role of ROS in acute cytokine-induced permeability changes in the GFB.