Stimulation of interleukin-6 promoter by parathyroid hormone, tumor necrosis factor α, and interleukin-1β in UMR-106 osteoblastic cells is inhibited by protein kinase C antagonists

Zsolt Nagy, Julie Radeff, Paula H. Stern*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

To investigate the level at which protein kinase C (PKC) regulates expression of interleukin-6 (IL-6) in osteoblastic cells, effects of several PKC antagonists and PKC down-regulation by phorbol ester were studied in UMR-106 osteoblastic cells that had been transiently transfected with a -224/+11-base pair (bp) IL-6 promoter coupled to a luciferase reporter. Parathyroid hormone (PTH) elicited a dose-dependent stimulation of the IL-6 promoter expression, with significant increases produced by 5 h of treatment with concentrations of PTH as low as 10-14 M. The increase in IL-6 promoter expression was inhibited by the PKC antagonists GF109203X, 30 nM to 1 μM, and calphostin C, 250 nM. Prior down-regulation of PKC with 100 nM phorbol-12,13-dibutyrate (PDBU) for 48 h inhibited the PTH effect as well as the smaller stimulatory effects elicited by tumor necrosis factor α (TNF-α), 10-9-10-8 M, and by IL-1β, 1-10 ng/ml. In contrast to these findings, the stimulatory effects of PTH, TNF-α, and IL-1β on the IL-6 promoter expression were enhanced by staurosporine. Treatment with GF109203X or down-regulation of PKC with PDBU prevented the stimulatory effects of staurosporine. PKC activity was increased by staurosporine. The findings with staurosporine are consistent with our earlier observations that this agent enhances the calcium signaling and bone resorption elicited by PTH. The studies support the role of PKC in the stimulatory effects of PTH, TNF-α, and IL-1β on IL-6 expression.

Original languageEnglish (US)
Pages (from-to)1220-1227
Number of pages8
JournalJournal of Bone and Mineral Research
Volume16
Issue number7
DOIs
StatePublished - 2001

Keywords

  • Cytokines
  • Interleukin-6
  • Osteoblast
  • Parathyroid hormone
  • Protein kinase C

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

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