The p38 mitogen-activated protein kinase pathway regulates interleukin-6 synthesis in response to tumor necrosis factor in osteoblasts

H. J. Chae, S. W. Chae, H. Y. Chin, B. G. Bang, S. B. Cho, K. S. Han, S. C. Kim, K. C. Tae, K. H. Lee, D. E. Kim, M. K. Im, S. J. Lee, J. Y. Chang, Y. M. Lee, H. M. Kim, H. H. Kim, Z. H. Lee, Hyung Ryong Kim

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37 Citations (Scopus)


The induction of interleukin-6 (IL-6), using a proinflammatory cytokine (tumor necrosis factor-α), was studied in a human osteoblast cell line (MG-63) in relation to p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB transcription factor. When added to MG-63 cells, tumor necrosis factor-α (TNF-α) had a stimulatory effect on the production of IL-6, and this elevation was significantly reduced by SB203580, a specific p38 MAPK inhibitor. In addition, the stimulation of IL-6 release was also reduced by pyrrolidine dithiocarbamate (PDTC) or NF-κB SN50, which has been reported to be a potent NF-κB inhibitor. Both the NF-κB inhibitors in the presence of SB203580 had a more inhibitory effect on IL-6 release. In this study, TNF-α stimulated NF-κB binding affinity as well as p38 MAP kinase activation, leading to the release of IL-6. However, the specific inhibitor of p38 MAPK, SB203580, had no effect on TNF-α-induced NF-κB activation and both NF-κB inhibitors failed to reduce the p38 MAPK activation in the TNF-α-stimulated osteoblasts. In addition, inhibition of p38 MAPK partially, but significantly, impaired TNF-α-regulated release of osteocalcin, an important differentiation marker in osteoblasts. These results strongly suggest that both p38 MAPK and NF-κB are required in TNF-α-induced IL-6 synthesis and that these two TNF-α-activated pathways can be primarily dissociated. Furthermore, p38 MAPK may play a significant role in differentiation in MG-63 cells.

Original languageEnglish
Pages (from-to)45-53
Number of pages9
Issue number1
Publication statusPublished - 2001
Externally publishedYes


  • Interleukin-6 (IL-6)
  • NF-κB inhibitor
  • Nuclear factor (NF)-κB
  • Osteoblast
  • p38 mitogen-activated protein kinase (MAPK)
  • Tumor necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology


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