title: Acidification changes affect the inflammasome in human nucleus pulposus cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Neurological Surgery, The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136 USA.
authors: Frank J
authors: FJ
authors: Brand
authors: Department of Neurological Surgery, The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136 USA.
authors: Mahtab
authors: M
authors: Forouzandeh
authors: Department of Neurological Surgery, The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136 USA.
authors: Harmanpreet
authors: H
authors: Kaur
authors: Biomechanics Research Laboratory, Department of Industrial Engineering, University of Miami, Coral Gables, FL 33146 USA.
authors: Francesco
authors: F
authors: Travascio
authors: Department of Neurological Surgery, The Miami Project to Cure Paralysis, Miller School of Medicine, University of Miami, Miami, FL 33136 USA ; Department of Neurological Surgery, Lois Pope LIFE Center, 1095 NW 14th Terrace, 3-25JJ, Miami, FL 33136-1060 USA.
authors: Juan Pablo
authors: JP
authors: de Rivero Vaccari
keywords: Caspase-1; Inflammasome; Inflammation; Innate Immunity; Intervertebral disc degeneration