CCAAT/enhancer binding protein β regulates the expression of tumor necrosis factor-α in the nucleus pulposus cells

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Abstract
Tumor necrosis factor alpha (TNF-α) is important in the process of intervertebral disc (IVD) degeneration because of its ability to regulate other inflammatory mediators in autocrine and paracrine fashions. The mechanism responsible for the cell type-specific regulation of TNF-α is not well known. CCAAT/enhancer binding protein β (C/EBP β) is one of the transcriptional factors that is implicated in TNF-α expression. However, it is not known whether cross talk occurs between C/EBP β and the TNF-α pathway in IVD cells. The expression and effect of the C/EBP β mRNA and protein in rat IVD cells was assessed using real-time reverse transcription polymerase chain reaction, immunohistochemical, and immunofluorescence analyses. We present data that show that the C/EBP β mRNA and protein were expressed in rat and human IVDs in vivo. We also found that the expression of TNF-α is regulated by the transcription factor C/EBP β in rat NP cells. The TNF-α promoter was suppressed completely in the presence of the ERK inhibitor PD98059 and the p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not in the presence of the JNK inhibitor SP600125. In addition, gain and loss of function analyses showed that the expression of TNF-α was regulated by C/EBP β through the MAPK pathways. These findings showed that C/EBP β acts as a potent pro-inflammatory mediator by inducing the TNF-α gene at the transcription and protein levels via the ERK1/2 and p38 pathways in rat NP cells. Our findings may open a new avenue toward the understanding of the cellular and molecular mechanisms of IVD cells. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:865–875, 2016.
Funding Information
  • Research and Study Program of the Tokai University Educational System General Research Organization
  • Grant-in-Aid for Scientific Research (KAKENHI)

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