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Prostaglandin E1 stimulates interleukin-6 secretion via protein kinase A in osteoblast-like cells
Y Watanabe-Tomita1, A Suzuki, Y Oiso
1First Department of Internal Medicine, Nagoya University, School of Medicine, Japan.
Abstract:
We investigated the effect of prostaglandin E1 (PGE1) on the secretion of interleukin-6 (IL-6) in osteoblast-like MC3T3-E1 cells. PGE1, which induced cAMP accumulation, stimulated IL-6 secretion time-dependently up to 48 h. The stimulative effect of PGE1 was dose-dependent in the range between 10 nM and 10 microM. Cholera toxin, an activator of Gs, stimulated IL-6 secretion in MC3T3-E1 cells. Forskolin, which directly activates adenylate cyclase, significantly induced IL-6 secretion in a dose-dependent manner in the range between 1 and 50 microM. Dibutyryl cAMP (Bt2-cAMP) stimulated IL-6 secretion time-dependently up to 48 h. The effect of Bt2-cAMP on IL-6 secretion was dose-dependent in the range between 0.1 and 3 mM. N-[2-(p-bromocinnamylamino) ethyl]-5-isoquinoline-sulfonamide (H-89), a potent and selective inhibitor of protein kinase A, which suppressed the IL-6 secretion induced by forskolin or Bt2-cAMP, significantly inhibited the IL-6 secretion induced by PGE1. These results indicate that PGE1 stimulates IL-6 secretion via the activation of protein kinase A in osteoblast-like cells.