Brand Frank J, Forouzandeh Mahtab, Kaur Harmanpreet, Travascio Francesco, de Rivero Vaccari Juan Pablo
Department of Neurological Surgery, The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136 USA.
Biomechanics Research Laboratory, Department of Industrial Engineering, University of Miami, Coral Gables, FL 33146 USA.
J Inflamm (Lond). 2016 Aug 24;13(1):29. doi: 10.1186/s12950-016-0137-0. eCollection 2016.
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.
白细胞介素（IL）-1β参与椎间盘退变的病理过程。在正常情况下，IL-1β以无活性形式（前体IL-1β）存在于细胞中。然而，在病理条件下，前体IL-1β被炎性小体转化为其活性形式（IL-1β），炎性小体是一种激活半胱天冬酶-1的先天性免疫反应的多蛋白复合物。在退变情况下，椎间盘会经历酸化增加的环境。然而，酸化对先天性免疫反应的影响仍未得到充分研究。
在此，我们通过对培养中暴露于不同pH水平的髓核细胞获得的蛋白质裂解物进行免疫印迹分析，研究了人髓核细胞中的pH变化如何影响炎性小体的激活。
在本研究中，我们发现，在髓核细胞中，随着酸化增加，炎性小体激活减少，这与活性IL-1β水平降低一致。然而，当用IL-1β处理细胞时，在测试的最低pH水平6.5时的这种效应被消除。
综上所述，这些发现表明，当刺激因素是酸化时，人类椎间盘通过IL-1β产生的炎症反应并非在髓核细胞中启动。
