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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
Author(s) -
Nagy Zsolt,
Radeff Julie,
Stern Paula H.
Publication year - 2001
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2001.16.7.1220
Subject(s) - staurosporine , protein kinase c , endocrinology , medicine , parathyroid hormone , calphostin , calphostin c , phorbol , tumor necrosis factor alpha , stimulation , biology , chemistry , kinase , microbiology and biotechnology , calcium
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.