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

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.