Involvement of protein kinase C activation in endothelin-1-induced secretion of interleukin-6 in osteoblast-like cells

Mitsuhiro Matsuno, Osamu Kozawa, Atsushi Suzuki, Haruhiko Tokuda, Takehiro Kaida, Hiroyuki Matsuno, Masayuki Niwa, Toshihiko Uematsu

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16 Citations (Scopus)

Abstract

We previously reported that endothelin-1 (ET-1) stimulates phospholipase D (PLD) independently of phosphoinositide hydrolysis in osteoblast-like MC3T3-E1 cells. In the present study, we examined the effect of ET-1 on the secretion of interleukin-6 (IL-6) and the involvement of protein kinase C (PKC) activation in the IL-6 secretion in these cells. ET-1 significantly stimulated IL-6 secretion time-dependently up to 72 h. The stimulative effect was dose-dependent in the range between 1 nM and 1 μM. BQ123, a selective antagonist of endothelin(A), (ET(A)) receptor, inhibited the ET-1-induced IL-6 secretion. On the contrary, BQ788, a selective antagonist of endothelin(B) (ET(B)) receptor, had no effect. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a PKC-activating phorbol ester, significantly stimulated IL-6 secretion. However, 4 α-phorbol 12,13-didecanoate, a PKC-nonactivating phorbol ester, did not affect IL-6 secretion. The effect of a combination of ET-1 and TPA on IL-6 secretion was not additive. Calphostin C, a specific PKC inhibitor, significantly inhibited the ET-1-induced IL-6 secretion. Both ET-1- and TPA-induced IL-6 secretion were reduced in PKC downregulated MC3T3-E1 cells. These results strongly suggest that ET-1 stimulates IL-6 secretion via ET(A) receptor in osteoblast-like cells and that PKC activation is involved in the ET-1-induced IL-6 secretion.

Original languageEnglish
Pages (from-to)107-111
Number of pages5
JournalCellular Signalling
Volume10
Issue number2
DOIs
Publication statusPublished - 02-1998

All Science Journal Classification (ASJC) codes

  • Cell Biology

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