Involvement of PKC-β in PTH, TNF-α, and IL-1β effects on IL-6 promoter in osteoblastic cells and on PTH-stimulated bone resorption

Julie M. Radeff, Zsolt Nagy, Paula H. Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Protein kinase C (PKC) has been shown to be activated by parathyroid hormone (PTH) in osteoblasts. Prior evidence suggests that this activation mediates responses leading to bone resorption, including production of the osteoclastogenic cytokine interleukin-6 (IL-6). However, the importance of specific PKC isozymes in this process has not been investigated. A selective antagonist of PKC-β, LY379196, was used to determine the role of the PKC-β isozyme in the expression of IL-6 in UMR-106 rat osteoblastic cells and in bone resorption in fetal rat limb bone organ cultures. PTH, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) induced translocation of PKC-α and -β1 to the plasma membrane in UMR-106 cells within 5 min. The stimulation of PKC-β1 translocation by PTH, TNF-α or IL-1β was inhibited by LY379196. In contrast, LY379196 did not affect PTH, TNF-α-, or IL-1β-stimulated translocation of PKC-α. PTH, TNF-α, and IL-1β increased luciferase expression in UMR-106 cells transiently transfected with a -224/+11 bp IL-6 promoter-driven reporter construct. The IL-6 responses were also attenuated by treatment with LY379196. Furthermore, LY379196 inhibited bone resorption elicited by PTH in fetal rat bone organ cultures. These results indicate that PKC-β1 is a component of the signaling pathway that mediates PTH-, TNF-α-, and IL-1β-stimulated IL-6 expression and PTH-stimulated bone resorption.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalExperimental Cell Research
Volume268
Issue number2
DOIs
StatePublished - Aug 15 2001

Keywords

  • Bone resorption
  • Interleukin-1β
  • Interleukin-6
  • Osteoblast
  • Parathyroid hormone
  • Protein kinase C isozymes
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Cell Biology

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