Prostaglandin f2 alpha stimulates interleukin-6 synthesis via
activation of pkc in osteoblast-like cells.
Kozawa, Osamu, Atsushi Suzuki, Haruhiko Tokuda, and Toshihiko Uematsu.
Department of Pharmacology, Gifu University School of Medicine,
Gifu 500; First Department of Internal Medicine, Nagoya University
School of Medicine, Nagoya 466; and Department of Internal Medicine,
Chubu National Hospital: National Institute for Longevity Sciences,
Obu, Aichi 474, Japan
APStracts 3:0202E, 1996.
In previous studies, we have reported that prostaglandin F2[alpha]
(PGF2[alpha]) stimulates phosphoinositide hydrolysis by phospholipase
C and phosphatidylcholine hydrolysis by phospholipase D in
osteoblast-like MC3T3-E1 cells. In the present study, we examined the
effect of PGF2[alpha] on synthesis of interleukin-6 (IL-6) and the
involvement of protein kinase C (PKC) activation in the IL-6
synthesis in these cells. PGF2[alpha] significantly stimulated IL-6
synthesis in a dose-dependent manner in the range between 10 nM and
10 [mu]M. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a PKC
-activating phorbol ester, induced IL-6 synthesis. On the contrary,
4[alpha]-phorbol 12,13-didecanoate, a PKC-nonactivating phorbol
ester, had no effect. The synthesis of IL-6 stimulated by a
combination of PGF2[alpha] and TPA was not additive. Staurosporine,
an inhibitor for protein kinases, which suppresed the TPA-induced IL
-6 synthesis, significantly inhibited the PGF2[alpha]-induced IL-6
synthesis. Calphostin C, a highly specific PKC inhibitor, also
suppressed the PGF2[alpha]-stimulated synthesis of IL-6. The effect
of PGF2[alpha] on IL-6 synthesis in PKC-down regulated cells was much
weaker than that in intact cells. These results strongly suggest that
PGF2[alpha] induces IL-6 synthesis via PKC activation in osteoblast
-like cells.
Received 9 April 1996; accepted in final form 13 September 1996.
APS Manuscript Number E176-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996