Acidification changes affect the inflammasome in human nucleus pulposus cells.
Acidification changes affect the inflammasome in human nucleus pulposus cells.
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DOI：
10.1186/s12950-016-0137-0
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
de Rivero Vaccari JP
中科院分区：
文献类型：
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作者：
Brand FJ 3rd;Forouzandeh M;Kaur H;Travascio F;de Rivero Vaccari JP
白细胞介素（IL）-1β参与椎间盘退变的病理过程。在正常条件下，IL-1β以非活性形式（pro-IL-1β）存在于细胞中。然而，在病理条件下，pro-IL-1β通过炎性体转化为其活性形式（IL-1β），炎性体是一种激活半胱天冬酶-1的先天免疫应答的多蛋白复合物。在退变的条件下，椎间盘经历增加的酸化环境。然而，酸化对先天免疫反应的影响仍然很少探索。在这里，我们已经研究了pH值的变化，在人类髓核细胞的影响炎症体激活的蛋白质裂解物的免疫印迹分析，从髓核细胞，暴露于不同的pH值水平的文化。在这项研究中，我们发现在髓核细胞中，随着酸化的增加，炎性小体活化减少，与活性IL-1β水平降低一致。然而，当用IL-1β处理细胞时，在pH 6.5（测试的最低pH水平）下的这种作用被消除。综上所述，这些发现表明，当刺激为酸化时，人椎间盘经历的通过IL-1β的炎症反应不是在髓核细胞中启动的。本文的在线版本（doi：10.1186/s12950-016-0137-0）包含补充材料，可供授权用户使用。
Interleukin (IL)-1β is involved in the pathology of intervertebral disc degeneration. Under normal conditions, IL-1β is present in cells in an inactive form (pro-IL-1β). However, under pathological conditions, pro-IL-1β is turned into its active form (IL-1β) by the inflammasome, a multi-protein complex of the innate immune response that activates caspase-1. Under conditions of degeneration, the disc experiences an environment of increased acidification. However, the implications of acidification on the innate immune response remain poorly explored. Here we have studied how pH changes in human nucleus pulposus cells affect inflammasome activation by immunoblot analysis of protein lysates obtained from nucleus pulposus cells that were exposed to different pH levels in culture. In this study, we have found that in nucleus pulposus cells, with increased acidification, there was a decrease in inflammasome activation consistent with lower levels of active IL-1β. However, this effect at a pH of 6.5, the lowest pH level tested, was abrogated when cells were treated with IL-1β. Taken together, these findings suggest that the inflammatory response through IL-1β experienced by the human disc is not initiated in nucleus pulposus cells when the stimulus is acidification. The online version of this article (doi:10.1186/s12950-016-0137-0) contains supplementary material, which is available to authorized users.